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PPIs for NUD, the story continues ▸
The efficacy of proton pump inhibitor (PPI) therapy in non-ulcer dyspepsia (NUD) is controversial. For example, there has been one positive (Blum et al, Gut 2000) and one negative (Wong et al, Gut 2002) randomised controlled trial published in Gut. Peura et al have conducted a randomised controlled trial comparing lansoprazole 30 mg once daily, lansoprazole 15 mg once daily, or placebo for eight weeks in 921 NUD patients. They defined NUD as patients with upper abdominal pain or discomfort as their main complaint who had a normal endoscopy. Patients with heartburn were included but not if this was the predominant problem. They reported that 44% experienced complete symptom resolution in their daily diaries with either dose of lansoprazole compared with 29% in the placebo group (number needed to treat = 6; 95% confidence intervals 4–15).
It is interesting that only 25% of patients had no baseline heartburn symptoms and it is possible that patients who responded to PPI therapy had atypical endoscopy negative reflux disease. Nevertheless, evidence is emerging that a modest number of patients with predominant upper abdominal pain and a normal endoscopy will respond to PPI therapy.
When all else fails? ▸
Sacral nerve stimulation was first used in the UK as a treatment for faecal incontinence six years ago, having been developed as an alternative to surgical reconstruction of the external anal sphincter. This paper describes the total UK experience during those six years. Three centres have carried out the procedure on a total of 46 patients (40 women). Improved continence was achieved in all but two patients. Episodes of faecal incontinence improved from a median (range) of 7.5 (1–78) to 1 (0–39) per week (p<0.001). Urgency also improved from a median of 1 (range 0–5) to 10 (1–15) minutes (p<0.001). Objective assessment of anal squeeze pressure and sensation to rectal distension also improved. There were also improvements in all subscales of the SF-36 quality of life questionnaire and in all four categories of the quality of life questionnaire of the American Society of Colon and Rectal Surgeons, according to lifestyle, coping/behaviour, depression/self perception, and embarrassment.
This technique is effective in improving faecal incontinence. It has not been compared formally with other surgical techniques but does offer good results of treatment of this extremely distressing symptom in selected patients.
Do ends justify means? ▸
Increased waist circumference is the most critical index of obesity that is strongly associated with insulin resistance and its metabolic consequences. Although both abdominal subcutaneous fat mass as well as visceral fat contribute to central obesity, it is not known whether one or both of the fat depots are involved in the pathogenesis of insulin resistance. Klein et al investigated seven women with type 2 diabetes (mean body mass index (BMI) 39.9 (5.6)) and eight women with normal glucose tolerance (BMI 35.1 (2.4)) before and 10–12 weeks after liposuction. Liposuction decreased the volume of abdominal subcutaneous fat by 28% and 44%, respectively. But this was not associated with increased insulin sensitivity (measured by euglycaemic hyperinsulinaemic clamp). Liposuction had no effect on hypertension, dyslipidaemia, or plasma concentration of adepokines, indicating that the decrease in subcutaneous adipose tissue (and thereby weight) alone does not favourably influence the metabolic consequences of central obesity.
Dixon et al, on the other hand, investigated the effect of weight loss following laparoscopic adjustable gastric band placement in 36 obese patients (BMI 47 (10.6)). After 25.6 (10) months of follow up, 34.0 (17) kg weight loss was achieved. This was associated with significant reduction in waist circumference and improvements in all of the components of the metabolic syndrome. Repeat liver biopsy showed marked improvement in steatosis, necroinflammation, as well as fibrosis, confirming that sustained weight loss can reverse insulin resistance and its consequences, including non-alcoholic fatty liver disease. The magnitude of histological improvement seen in this study should be considered in the context that 17/36 patients were selected to have a repeat biopsy because of advanced changes in the index biopsy, thus introducing a potential bias.
Together, these two studies highlight the importance of visceral fat in the pathogenesis of the metabolic syndrome and the value of sustained weight loss achieved through negative energy balance in the management of this condition.
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