Gout in the UK and Germany: prevalence, comorbidities and management in general practice 2000-2005.

OBJECTIVE: To investigate and compare the prevalence, comorbidities and management of gout in practice in the UK and Germany. METHODS: A retrospective analysis of patients with gout, identified through the records of 2.5 million patients in UK general practices and 2.4 million patients attending GPs or internists in Germany, using the IMS Disease Analyzer. RESULTS: The prevalence of gout was 1.4% in the UK and Germany. Obesity was the most common comorbidity in the UK (27.7%), but in Germany the most common comorbidity was diabetes (25.9%). The prevalence of comorbidities tended to increase with serum uric acid (sUA) levels. There was a positive correlation between sUA level and the frequency of gout flares. Compared with those in whom sUA was <360 micromol/l (<6 mg/dl), odds ratios for a gout flare were 1.33 and 1.37 at sUA 360-420 micromol/l (6-7 mg/dl), and 2.15 and 2.48 at sUA >530 micromol/l ( >9 mg/dl) in the UK and Germany, respectively (p<0.01). CONCLUSIONS: The prevalence of gout in practice in the UK and Germany in the years 2000-5 was 1.4%, consistent with previous UK data for 1990-9. Chronic comorbidities were common among patients with gout and included conditions associated with an increased risk for cardiovascular disease, such as obesity, diabetes and hypertension. The importance of regular monitoring of sUA in order to tailor gout treatment was highlighted by data from this study showing that patients with sUA levels >or=360 micromol/l (>or=6 mg/dl) had an increased risk of gout flares.

Triple-helical DNA as a reversible block of the branch point in a partially symmetrical DNA four-arm junction.

DNA branch migration is a fundamental process in genetic recombination. A new model system has been developed for studying branch migration in a small synthetic four-arm junction. A mathematical method for describing branch-point movement by discrete steps in such junctions is also presented. The key to our experimental system is the ability to fix the location of the branch point during the assembly of the junction with a reversible block. The block is provided by a short oligonucleotide that forms triplex DNA adjacent to the initial location branch point at low pH. Raising the pH causes the triplex strand to dissociate, making the branch point free to migrate. Once mobile, the branch point can run off the end of the junction. The time-course for this runoff is consistent with a random walk of the branch point. If it is assumed that one migration step moves the branch point one base-pair, the time-course gives a rate constant for one step of 1.4 second-1 at 37 degrees C in 10 mM MgCl2, 50 mM NaCl. These values are consistent with other measurements of non-enzymatic branch migration. We have also monitored the spread of the branch points directly with T4 endonuclease VII. Using EcoRI restriction endonuclease, we have shown that the binding of this protein to the arms of the junction essentially blocks branch migration through the binding site. In these experiments Ca2+ replaces Mg2+, and the enzyme does not cleave the DNA. In vivo there must be a special process to get branch points to migrate past bound proteins.

Negative affect and the experience of chronic pain.

Although it is clear from previous research that pain is associated with negative affect, the relative contribution of specific affective dimensions, e.g. depression, anxiety and anger, to the subjective experience of chronic pain is unclear. The literature is also mixed concerning the relative importance of state versus trait influences in the experience of chronic pain. The present study analyzed the ability of anxiety, anger, and depression (as measured by the State-Trait Personality Inventory, State-Trait Anger Expression Inventory, and the Beck Depression Inventory, respectively) to predict self-report of clinical pain as indicated by the McGill Pain Questionnaire (MPQ) in a sample of 60 chronic pain patients. The results of stepwise regression analyses consistently demonstrated that the state measures were more strongly related to MPQ pain ratings than trait measures. These data suggest support for the hypothesis that chronic pain adversely impacts mood rather than the opposing hypothesis that negative mood is a predisposing factor in the development of chronic pain. Furthermore, different aspects of the state emotional experience were found to be related to different components of pain report. The results of this study also suggest that attributional processes could be an important component of the relationship between negative mood and the experience of pain.

The effects of lesions to ascending noradrenergic neurons on discrimination learning and performance in the rat.

Three experiments examined the effect of central noradrenergic depletion on the acquisition and performance of a temporal discrimination in auditory or visual modalities. In Experiment 1, 6-hydroxydopamine-induced lesions of the dorsal noradrenergic bundle significantly retarded acquisition compared to a similarly lesioned ventral noradrenergic bundle-group, two sham-operated and one unoperated control group. In Experiment 2, the acquisition impairment produced in the dorsal noradrenergic bundle group was replicated, for both auditory and visual modalities, by lesions depleting hippocampal and neocortical noradrenaline by over 80%. In rats subsequently switched to discriminations involving the unfamiliar modality, the dorsal-bundle lesion also impaired acquisition several weeks after surgery. Experiment 3 showed significantly impaired performance in rats with dorsal bundle lesions when training prior to surgery had not resulted in better than chance performance. In rats previously trained to criterion, the dorsal bundle lesion transiently, but non-significantly, impaired performance. In rats performing better than chance, but not having reached criterion, there were no significant effects of the dorsal bundle lesion. Subsequent manipulations of deprivation and difficulty of discrimination in general failed to distinguish between the dorsal bundle lesion and sham-groups, suggesting that the acquisition impairment did not result from simple sensory or motivational effects. Reducing the interstimulus interval did impair the dorsal bundle group more than controls. However, there was no evidence of altered "distractibility" in the lesioned group when the alternative modality was introduced as a distractor. The results are discussed in terms of other acquisition deficits shown by rats with central noradrenaline depletion and their significance for determining the functions of the projections from the locus caeruleus via the dorsal noradrenergic bundle to the neocortex and hippocampus.

Contrasting interactions of pipradrol, d-amphetamine, cocaine, cocaine analogues, apomorphine and other drugs with conditioned reinforcement.

The effects of various psychomotor stimulant drugs and drugs outside this class were examined on the efficacy of stimuli previously paired with reinforcement or reward (conditioned reinforcers, CR) in controlling responding. Pipradrol (5-45 mumol/kg), d-amphetamine (1.25-15.0 mumol/kg), and the cocaine analogues WIN 35,428 (0.1-30.0 mumol/kg) and in one of two determinations WIN 35,065-2 (0.1-29.0 mumol/kg) all generally increased responding on a lever providing CR, but did not change or decreased responding on a lever providing no CR (NCR). Cocaine (5-125 mumol/kg) and chlordiazepoxide (3.75-60.0 mumol/kg) had no significant effects. Morphine (3.2-32.0 mumol/kg) and alpha-flupenthixol (0.02-2.0 mumol/kg) generally reduced responding on both levers. Apomorphine (0.1-1.0 mumol/kg) generally increased responding on both levers. Neurochemical data showed that d-amphetamine was generally more potent than pipradrol in its effects on in vitro monoamine uptake and release.