Efficacy of an intermittent energy restriction diet in a primary care setting.

PURPOSE: Intermittent energy restriction (IER) is a popular weight loss (WL) strategy; however, its efficacy in clinical practice remains unknown. The present study compared the effects of IER compared to continuous energy restriction (CER) on WL and cardiometabolic risk factors in primary care. METHODS: A (self-selected) cohort study was conducted at the Rotherham Institute for Obesity (RIO), a primary care-based weight management service. 197(24% male) obese patients volunteered to participate and selected their diet group. IER participants (n = 99) consumed ~ 2600 kJ for two days/week. CER participants (n = 98) restricted their diet by ~ 2100 kJ/day below estimated requirements. Both interventions were delivered alongside RIO standard care. Changes in anthropometry and cardiometabolic disease risk markers (fasting biochemistry and blood pressure) were assessed after a 6-month intervention period and then participants were followed up again 6 months later (month 12). RESULTS: 27 IER patients (27%) and 39 CER patients (40%) completed the 6-month weight loss phase. Among completers, mean (SEM) WL was greater in the IER group at 6 months (5.4 ± 1.1% versus 2.8 ± 0.6%; p = 0.01), as were reductions in fat mass (p < 0.001) and improvements in systolic blood pressure (p < 0.001). Fasting insulin (p = 0.873) and diastolic blood pressure (p = 0.701) were reduced similarly in both groups. However, in the IER group, changes in anthropometry and blood pressure in the IER group had reverted to baseline by 12-month follow-up, whilst the CER group maintained weight loss but showed an increase in blood pressure. CONCLUSIONS: Among completers, IER resulted in superior short-term changes in anthropometry and some cardiometabolic risk factors. However, rates of attrition and weight regain were higher compared with standard care, providing important insights in the implementations of IER within a "real-life" NHS setting. TRIAL REGISTRATION NUMBER: ISRCTN31465600.

Human filarial Wolbachia lipopeptide directly activates human neutrophils in vitro.

The host inflammatory response to the Onchocerca volvulus endosymbiont, Wolbachia, is a major contributing factor in the development of chronic pathology in humans (onchocerciasis/river blindness). Recently, the toll-like pattern recognition receptor motif of the major inflammatory ligands of filarial Wolbachia, membrane-associated diacylated lipoproteins, was functionally defined in murine models of pathology, including mediation of neutrophil recruitment to the cornea. However, the extent to which human neutrophils can be activated in response to this Wolbachia pattern recognition motif is not known. Therefore, the responses of purified peripheral blood human neutrophils to a synthetic N-terminal diacylated lipopeptide (WoLP) of filarial Wolbachia peptidoglycan-associated lipoprotein (PAL) were characterized. WoLP exposure led to a dose-dependent activation of healthy, human neutrophils that included gross morphological alterations and modulation of surface expressed integrins involved in tethering, rolling and extravasation. WoLP exposure induced chemotaxis but not chemokinesis of neutrophils, and secretion of the major neutrophil chemokine, interleukin 8. WoLP also induced and primed the respiratory burst, and enhanced neutrophil survival by delay of apoptosis. These results indicate that the major inflammatory motif of filarial Wolbachia lipoproteins directly activates human neutrophils in vitro and promotes a molecular pathway by which human neutrophils are recruited to sites of Onchocerca parasitism.

The cost-effectiveness of the LighterLife weight management programme as an intervention for obesity in England.

LighterLife Total is a very low calorie diet total dietary replacement weight reduction programme that provides Foodpacks, behavioural change therapy and group support appropriate for people with a body mass index of 30 kg m(-2) or above. A model was built to assess the cost-effectiveness of LighterLife Total, compared with (i) no treatment, Counterweight, Weight Watchers and Slimming World, as a treatment for obesity in those with a body mass index of 30 kg m(-2) or above, and (ii) no treatment, gastric banding and gastric bypass in those with a body mass index of 40 kg m(-2) or above. Change in body mass index over time was modelled, and prevalence of comorbidities (diabetes, coronary heart disease and colorectal cancer) was calculated. Costs (of intervention and treatment for comorbidities) and quality-adjusted life years were calculated. LighterLife Total was cost-effective against no treatment, Counterweight, Weight Watchers and Slimming World in the 30+ kg m(-2) group (incremental cost-effectiveness ratios: £11 895, £12 453, £12 585 and £12 233, respectively). In the 40+ kg m(-2) group, LighterLife Total was cost-effective against no treatment (incremental cost-effectiveness ratio: £4356), but less effective than gastric banding and bypass.

Long-term weight loss maintenance and management following a VLCD: a 3-year outcome.

BACKGROUND: Effective weight loss treatment is important as obesity has severe health and socioeconomic repercussions. Emerging evidence suggests that rapid initial weight loss results in better long-term weight loss maintenance. This remains controversial and contradicts current recommendations for slower weight loss. AIM: To determine the effect of a very low calorie diet (VLCD) with group-based behaviour therapy on weight loss and long-term weight management by means of a retrospective database analysis. METHODS: Data for this retrospective analysis included participants who embarked on the LighterLife Total VLCD programme between 2007 and 2010, and whose weights at baseline and at least 12 months were available (n = 5965). RESULTS: Data were available for 5965 individuals at 1 year, 2044 at 2 years and 580 at 3 years. At baseline, the majority of individuals were Caucasian (n = 5155), female (n = 5419), ≥ 40 years old (n = 4272), 49% were within the body mass index (BMI) range of 30-35 kg/m(2) while 51% had a BMI > 35 kg/m(2) . The average initial weight of the whole cohort was 99.1 kg (SD 16.6). Initial weight and BMI at entry onto programme, as well as numbers of weeks of weight loss were all significantly associated with weight loss achieved on the first weight loss attempt. Weight lost during the initial weight loss phase was the only factor, which was significantly associated with percentage weight loss maintenance for years 1, 2, and 3. CONCLUSION: The findings of this retrospective analysis suggest that provided a longer term weight loss management programme is adhered to, large amounts of initial weight loss can result in important longer term weight loss maintenance in motivated individuals.

Weight loss for individuals with type 2 diabetes following a very-low-calorie diet in a community-based setting with trained facilitators for 12 weeks.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Approximately 80% of people with type 2 diabetes mellitus (T2DM) are overweight or obese. Weight loss produces numerous benefits in T2DM. People with T2DM have difficulty losing and maintaining weight. WHAT THIS STUDY ADDS: Provision of a very-low-calorie diet (VLCD) with group support and behaviour therapy for patients with T2DM is feasible within a community-based setting with trained facilitators. VLCD approaches for weight management in T2DM can achieve more than 90% of weight loss as compared with obese individuals without T2DM. Identification of the need to investigate the full impact of this approach in patients with T2DM by assessing changes in glycaemia, liver function and medication. Approximately 80% of people with type 2 diabetes mellitus (T2DM) are overweight or obese, and obesity compounds the cardiovascular risk of T2DM. The aim of this retrospective study was twofold: first, to investigate whether a 12-week community-based very-low-calorie diet (VLCD) programme can result in important weight loss; and second, to investigate any potential difference in the weight loss achieved using this community-based approach in individuals with and without T2DM. Three hundred and fifty-five participants with T2DM were matched for age, body mass index (BMI) and gender to participants without T2DM (total cohort comprised 204 males: 506 females (mean ± standard deviation); age (years) 54.0 ± 9.1; BMI (kg m(-2) ) 41.6 ± 8.1; weight (kg) 116.1 ± 25.1). The programme included a daily intake of 550 kcal in addition to group support and behaviour therapy provided by trained facilitators within a community-based setting. After 12 weeks, there was significant weight loss within each group when compared with baseline (T2DM: 115.0 ± 24.4 kg vs. 96.7 ± 21.4 kg, P < 0.0001; non-T2DM: 117.2 ± 25.8 kg vs. 97.3 ± 22.2 kg, P < 0.0001). At 12 weeks, weight change (-18.3 ± 7.3 kg vs. -19.9 ± 7.0 kg, P = 0.012) and BMI change (-6.7 ± 2.9 kg m(-2) vs. -7.1 ± 2.1 kg m(-2) , P = 0.011) were significantly less in the T2DM group when compared with the non-T2DM group. Our results suggest that the use of VLCD approaches for weight management in T2DM can achieve more than 90% of the weight loss seen in obese individuals without T2DM.

Resistant starch improves insulin sensitivity in metabolic syndrome.

AIMS: Diets rich in non-viscous fibre are linked to a reduced risk of both diabetes and cardiovascular disease; however, the mechanism of action remains unclear. This study was undertaken to assess whether chronic consumption of this type of fibre in individuals with the metabolic syndrome would improve insulin sensitivity via changes in ectopic fat storage. METHODS: The study was a single-blind, randomized, parallel nutritional intervention where 20 insulin resistant subjects consumed either the fibre supplement (resistant starch) (40 g/day) or placebo supplement (0 g/day) for 12 weeks. Insulin sensitivity was measured by euglycaemic-hyperinsulinaemic clamp and ectopic fat storage measured by whole-body magnetic resonance spectroscopy. RESULTS: Resistant starch consumption did not significantly affect body weight, fat storage in muscle, liver or visceral depots. There was also no change with resistant starch feeding on vascular function or markers of inflammation. However, in subjects randomized to consume the resistant starch, insulin sensitivity improved compared with the placebo group (P = 0.023). Insulin sensitivity correlated significantly with changes in waist circumference and fat storage in tibialis muscle and to a lesser extent to visceral-to-subcutaneous abdominal adipose tissue ratio. CONCLUSION: Consumption of resistant starch improves insulin sensitivity in subjects with the metabolic syndrome. Unlike in animal models, diabetes prevention does not appear to be directly related to changes in body adiposity, blood lipids or inflammatory markers. Further research to elucidate the mechanisms behind this change in insulin sensitivity in human subjects is required.

Non-haem iron transport in the rat proximal colon.

BACKGROUND: Only 10% of dietary iron is absorbed in the duodenum which implies that 90% (approximately 9 mg day(-1)) reaches the lower small intestine and colon. Therefore the purpose of this study was to assess the iron transport capacity of the rat proximal colon and to determine whether iron absorption is regulated by changes in dietary iron content. MATERIALS AND METHODS: Rats were fed for 14 days on either iron adequate (44 mg Fe kg(-1) diet) or iron-deficient (< 0.5 mg Fe kg(-1) diet) diets. The 59Fe transport across the colonic epithelium and its subsequent appearance in the blood were measured in vivo. In separate studies the colon was excised and used to measure divalent metal transporter expression. RESULTS: Divalent metal transporter (DMT1) was expressed at the apical membrane of the surface epithelium in rat proximal colon. In animals fed an iron-deficient diet, DMT1 mRNA and protein expression were increased. This was accompanied by a significant increase in tissue 59Fe uptake. CONCLUSIONS: The proximal colon can absorb non-haem iron from the intestinal lumen. The purpose of this mechanism remains to be elucidated.

Critical comparison of molecular genotyping methods for detection of drug-resistant Plasmodium falciparum.

We have critically evaluated 3 techniques for the detection of mutations conferring drug resistance of Plasmodium falciparum, using samples containing known numbers of well-characterized parasites and artificial mixtures of these parasites at known proportions. We compared the sensitivity and specificity of mutation-specific polymerase chain reaction (MS-PCR), polymerase chain reaction followed by restriction enzyme digestion at polymorphic sites (PCR/RFLP), and a dot-blot/probe hybridization technique, for detection of point mutations at nucleotide 323 of the P. falciparum dihydrofolate reductase gene (dhfr) that confer resistance to the antimalarial drug pyrimethamine. We have also investigated the benefits in terms of sensitivity and reproducibility of the incorporation of radiolabelled nucleotides into the PCR/RFLP assay. We found that MS-PCR was very sensitive--at least 10 parasites could be detected in a sample--but non-specific amplification resulted in erroneous typing of some samples. PCR/RFLP was less sensitive; 10 parasites per sample could not always be detected, but the technique was specific. The addition of radiolabelled nucleotides to the assay did not markedly improve the sensitivity but the results were easier to read and there was less subjectivity in scoring the results. The dot-blot/probe hybridization technique was specific and sensitive, with similar levels of specificity and sensitivity to PCR/RFLP. On balance, the dot-blot/probe hybridization technique seems best suited to large-scale epidemiological surveys of genes associated with antimalarial drug resistance.

Use of an orally administered combined sugar solution to evaluate intestinal absorption and permeability in cats.

OBJECTIVE: To evaluate intestinal permeability and absorption in healthy cats in association with diet and normal intestinal microflora. ANIMALS: 6 healthy domestic shorthair cats. PROCEDURE: A sugar solution containing D-xylose, 30-methyl-D-glucose, L-rhamnose, lactulose, and 51Cr-EDTA was administered intragastrically to healthy cats, and urinary excretion of ingested sugars was determined 5 hours after administration. After the same cats had received metronidazole for 1 month, the study was repeated. A final study was performed while cats were maintained on a new diet differing in composition and processing. RESULTS: Lactulose-to-rhamnose ratios, reflecting intestinal permeability, were higher in cats, compared with values for humans or dogs, and values obtained before and after metronidazole administration (mean +/- SEM; before, 0.40 +/- 0.08; after, 0.45 +/- 0.09) were not significantly different. Intestinal absorption also was unaltered after antibiotic administration, and the xylose-to-glucose ratio was 0.70 +/- 0.03 before and 0.71 +/- 0.06 after metronidazole administration. Sugar recovery did not differ significantly while cats were maintained on canned or dry food. CONCLUSIONS AND CLINICAL RELEVANCE: Reference ranges were established for the percentage urinary recovery of orally administered D-xylose, 3-0-methyl-D-glucose, L-rhamnose, lactulose, and 51Cr-EDTA obtained after 5 hours in healthy cats. The intestines of cats appear to be more permeable than those of other species, although the normal bacterial microflora does not appear to influence the integrity or function of the feline intestine, because values obtained for the measured variables before or after antibiotic administration were not significantly different. In addition, differences were not detected when the diet was completely altered.

Comparison of the bacterial flora of the duodenum in healthy cats and cats with signs of gastrointestinal tract disease.

OBJECTIVE: To determine whether a colony environment predisposes healthy cats to high bacterial counts, including counts of obligate anaerobes, in the duodenum and whether increased numbers of bacteria could be found in the duodenum of cats with signs of chronic gastrointestinal tract disease. DESIGN: Prospective study. ANIMALS: 20 healthy control cats (10 from a colony environment and 10 pet cats) and 19 cats with a history of chronic gastrointestinal tract disease. PROCEDURE: Undiluted duodenal fluid was quantitatively and qualitatively assessed by bacteriologic culture under aerobic and anaerobic conditions. Serum concentrations of cobalamin and folate were also measured. RESULTS: Significant differences were not detected in the numbers of bacteria found in the duodenum of cats housed in a colony environment, compared with pet cats fed an identical diet prior to sampling. All healthy cats were, therefore, combined into 1 control group. Compared with healthy cats, cats with clinical signs of gastrointestinal tract disease had significantly lower counts of microaerophilic bacteria, whereas total, anaerobic, and aerobic bacterial counts were not significantly different. None of the cats with disease had total bacterial counts higher than expected from the range established in the control cats. Differences were not detected in regard to serum folate or cobalamin concentrations between diseased and healthy cats. CONCLUSIONS AND CLINICAL RELEVANCE: These findings indicated that healthy colony cats and pet cats have high numbers of bacteria in the duodenum, including high numbers of obligate anaerobes. Our findings also suggest that bacterial overgrowth in the small intestine is not a common clinical syndrome in cats with chronic nonobstructive gastrointestinal tract disease.

Effects of oral administration of metronidazole on small intestinal bacteria and nutrients of cats.

OBJECTIVE: To determine effects of oral administration of metronidazole on the number and species of duodenal bacteria and selective nutrients of cats. ANIMALS: 6 healthy domestic shorthair cats. PROCEDURE: Undiluted duodenal fluid was obtained for quantitative and qualitative bacterial culture to determine species and number of bacteria in healthy cats. Blood samples were assayed for taurine, total protein, albumin, cobalamin, and folate concentrations. Cats then were given metronidazole (20 mg/kg of body weight, PO, q 12 h) for 1 month, after which bacterial cultures and serum assays of nutrients were repeated. Nine months after cessation of antibiotic treatment, duodenal bacteria were re-evaluated and serum was assayed for total protein, albumin, cobalamin, and folate concentrations. RESULTS: Oral administration of metronidazole caused a significant decrease in aerobic and anaerobic bacterial counts in the duodenum of healthy cats, accompanied by emergence of Streptococcus spp and Corynebacterium spp. Serum concentrations of cobalamin and albumin increased when duodenal bacterial counts were decreased, although changes in folate or taurine concentrations were not detected. Measured variables did not differ, when comparing results obtained before and 9 months after cessation of metronidazole. CONCLUSIONS AND CLINICAL RELEVANCE: Oral administration of metronidazole decreased the number of aerobic bacteria and altered indigenous flora in the small bowel of cats. Normal duodenal flora appeared to be stable, because species of bacteria were re-established by 9 months after cessation of metronidazole. Bacterial flora appeared to have an impact on nutrients, because albumin and cobalamin increased during antibiotic administration and returned to preadministration concentrations after cessation of the antimicrobial.

Small intestinal bacterial overgrowth.

It is clear that the exact definition of small intestinal bacterial overgrowth (SIBO) needs to be reappraised in veterinary medicine. Antibiotic responsive enteropathies due to SIBO must be distinguished from those that are not associated with SIBO, such as those caused by a lack of immune tolerance. Once appropriate definitions and criteria for diagnosis are in place, the wide variety of diagnostic procedures that may facilitate the diagnosis can be evaluated with respect to their sensitivity and specificity, and statements about the prevalence and significance of this disorder can be made.

A comparison of endoscopic and surgical collection procedures for the analysis of the bacterial flora in duodenal fluid from cats.

In order to assess an endoscopic collection procedure, populations of bacteria in duodenal fluid from seven adult cats were compared in paired samples obtained by endoscopy and direct needle aspiration during laparotomy. Each sample of duodenal juice was subjected to quantitative and qualitative culture of bacteria under both aerobic and anaerobic conditions. There were no significant differences in total numbers or individual species of bacteria comparing the two collection procedures. These findings indicate that collection of duodenal juice by endoscopy using the procedure described provides a representative sample of small bowel fluid for the assessment of the bacterial flora. Therefore, there appears to be no need for more invasive or complicated sampling techniques when quantitative and qualitative culture of duodenal juice is indicated as part of an investigation of small bowel disease in cats.

Predictors of intracranial pathologic findings in patients who seek emergency care because of headache.

BACKGROUND: Clinical criteria to select patients with headache in whom structural diagnostic studies (computed tomography) have a high yield disclosing intracranial pathologic findings, independent of abnormal findings on neurologic examination, have not been defined. OBJECTIVE: To determine which clinical characteristics predict the presence of intracranial pathologic findings, independently of neurologic examination, in patients with headache. DESIGN: Case-control, consecutive sample. SETTING: Major metropolitan trauma center emergency department. PATIENTS AND MATERIALS: Hospital records of 139 hospitalized and 329 randomly selected patients from 1720 nonhospitalized adult patients, consecutively evaluated for headache in the emergency department, were reviewed. Demographic data, clinical characteristics of the headache, results of neurologic and physical examinations, and diagnostic radiologic and laboratory results were correlated with final diagnosis and outcome at 6 months after emergency department visit. DATA ANALYSIS: Nonparametric statistical analysis. RESULTS: Intracranial pathologic findings were found in 18 (3.8%) of 468 patients. Acute onset and occipitonuchal location of headache, presence of associated symptoms, and patient age of 55 years or older were significantly associated with the finding of intracranial pathology, independently of the findings from neurologic examination. Abnormal findings on neurologic examination alone, whether focal or nonfocal, had a highly significant association and a positive predictive value for intracranial pathology of 39%. CONCLUSIONS: Abnormal results from neurologic examination are the best clinical parameters to predict structural intracranial pathology; however, in patients 55 years or older with headache of acute onset located in the occipitonuchal region that has associated symptoms, computed tomographic scan of the head is justified as part of their clinical evaluation independently of the findings of the neurologic examination.

Releasable tissue plasminogen activators in ischemic stroke.

To determine if patients who suffer atherothrombotic ischemic stroke have altered release of tissue plasminogen activator (t-PA), we measured levels in 22 patients within 24 h of onset of symptoms and 1-2 months later. t-PA levels were measured in blood samples by using a colorimetric method after subjecting the plasma to euglobulin fractionation and reacting it with plasminogen and plasmin substrate. Values from a group of normal volunteers previously studied were used as controls. Individual variability in t-PA levels was found acutely and in the recovery phase. During the latter, patients' levels were significantly higher than controls, which was not the case in the acute phase. There was no correlation among t-PA levels, size of cerebral infarct, and patients' clinical status. We propose that endothelial repair and a rebound in endogenous fibrinolytic activity in the absence of peripheral venous disease are responsible for the late (recovery phase) elevation in t-PA.

The performance of children with auditory perceptual disorders on a time-compressed speech discrimination measure.

A time-compressed version of the PB-K 50 speech discrimination measure was administered to 20 children diagnosed as displaying auditory perceptual disorders. Results indicated that these children performed equally well at both 0 and 30% time compression. Performance decreased significantly at 60% time compression. Comparison of the results with normative data indicated that performance of the two groups of children was similar at the 30% time compression condition but that children with auditory perceptual disorders performed poorer at both 0 and 60% time compression. The results were discussed relative to short-term memory abilities.