THE TREATMENT OF ACUTE AND CHRONIC VAGINAL CANDIDOSIS

Vaginal candidosis is one of the most common infections of the vagina and the first accredited record of the disease appeared in 1849. Over the years the terms ‘candidiasis’ and ‘candidosis’ have been used, but it is generally accepted now that the terms are synonymous, and the term most commonly in use today is ‘candidosis’. Mainly caused by the yeast Candida albicans, the condition is characterised by intense inflammation of the vaginal mucosa and a curdy, off-white discharge; it is often associated with severe vulval itching and possibly burning pain. The severity of symptoms seems to vary greatly from patient to patient and the reason for this is unclear. It is suggested that in some patients there may be an element of hypersensitivity. Vaginal candidosis may occur in children but is most common in adults and only sometimes affects the elderly. The majority of women will suffer at least one attack of vaginal candidosis during their lifetime, and there are several predisposing factors such as diabetes, pregnancy and antibiotics. Some authorities consider the condition more frequent in those taking oral contraceptives or other hormones.     

Nutrient-specific modulation of gastric mechanosensitivity in patients with functional dyspepsia

Intraduodenal lipid infusion induces symptoms and increases sensitivity to gastric distension in patients with functional dyspepsia. To test whether these effects are specific for lipid, we compared the effects of intraduodenal infusions of either lipid or glucose on symptoms and gastric sensory and motor responses to gastric distension. Eighteen dyspeptic patients and nine controls were studied. The stomach was distended with a flaccid bag during isocaloric infusions (1 kcal/ml) of saline and either 10% Intralipid (nine patients) or 26.7% glucose (nine patients) into the duodenum. Dyspeptic symptoms and sensory thresholds for epigastric fullness and discomfort were assessed. Gastric pressure profiles during distensions were similar during lipid and glucose infusions in patients and controls, but both were significantly lower than during saline infusion. Lower volumes were required to induce fullness and discomfort in the patients compared with the controls. In the controls, the threshold volumes required to induce fullness and discomfort were greater during infusion of lipid and glucose than during saline infusion, but in the patients, the threshold volumes were increased during glucose infusion but further reduced during lipid infusion. Moreover, in the patients, nausea was more common during lipid than glucose infusion and did not occur during saline. The controls did not experience any symptoms during any infusion. In conclusion, intraduodenal lipid but not glucose sensitizes the stomach to distension in patients with functional dyspepsia but not in controls.     

USING MENDELIAN RANDOMISATION TO INFER CAUSALITY IN DEPRESSION AND ANXIETY RESEARCH

Depression and anxiety co‐occur with substance use and abuse at a high rate. Ascertaining whether substance use plays a causal role in depression and anxiety is difficult or impossible with conventional observational epidemiology. Mendelian randomisation uses genetic variants as a proxy for environmental exposures, such as substance use, which can address problems of reverse causation and residual confounding, providing stronger evidence about causality. Genetic variants can be used instead of directly measuring exposure levels, in order to gain an unbiased estimate of the effect of various exposures on depression and anxiety. The suitability of the genetic variant as a proxy can be ascertained by confirming that there is no relationship between variant and outcome in those who do not use the substance. At present, there are suitable instruments for tobacco use, so we use that as a case study. Proof‐of‐principle Mendelian randomisation studies using these variants have found evidence for a causal effect of smoking on body mass index. Two studies have investigated tobacco and depression using this method, but neither found strong evidence that smoking causes depression or anxiety; evidence is more consistent with a self‐medication hypothesis. Mendelian randomisation represents a technique that can aid understanding of exposures that may or may not be causally related to depression and anxiety. As more suitable instruments emerge (including the use of allelic risk scores rather than individual single nucleotide polymorphisms), the effect of other substances can be investigated. Linkage disequilibrium, pleiotropy, and population stratification, which can distort Mendelian randomisation studies, are also discussed.     

Longitudinal study of levodopa in Parkinson's disease: Effects of the advanced disease phase

Thirty‐four patients have been studied from the time of initiation of pharmacological treatment in a long‐term prospective study of levodopa effects and disease progression in Parkinson's disease. Objective motor scoring of the response to levodopa in defined off states was performed every 3 years. The mean time from the initiation of levodopa treatment to the most recent measurements was 18.2 years. Of 8 patients who are still alive, only 3 had none of the features of the advanced disease phase (dementia, hallucinations, frequent falling). Off‐phase motor function worsened at a yearly rate of 1.9% of the maximum disability score, although the plots of the serial scores showed that the magnitude of the levodopa response is well preserved. There was little difference in the rate of progression between patients with tremor‐dominant and non‐tremor‐dominant motor subtypes. Those who developed dementia had more rapid deterioration of motor scores, with significantly worse off‐phase (P = .008) and on‐phase (P = .03) motor function. A graph of serial scores of patients who have died, aligned for time of death, showed an upward curving trend of motor disability in the last 5 years of the disease course. Its advanced phase may reveal that Parkinson's disease has an exponential pattern of progression. © 2013 Movement Disorder Society