Long-term outcomes of index cryoballoon ablation or point-by-point radiofrequency ablation in patients with atrial fibrillation and systolic heart failure.

Catheter ablation is an established effective approach for the treatment of atrial fibrillation (AF) in patients with heart failure, however, the role of cryoablation in this setting is unclear. Procedural success and left ventricular systolic dysfunction (LVEF) improvement in patients with LVEF ≤ 45% undergoing index catheter ablation with cryoablation were evaluated. Freedom from AF recurrence was seen in 43% rising to 59% following repeat procedure. There were significant improvements in LVEF and functional status at long-term follow-up. Results were comparable to a contemporaneous cohort of heart failure patients undergoing index ablation with radiofrequency ablation. Cryoablation is an effective first-line AF ablation approach in the setting of heart failure.

A consideration of biomarkers to be used for evaluation of inflammation in human nutritional studies.

To monitor inflammation in a meaningful way, the markers used must be valid: they must reflect the inflammatory process under study and they must be predictive of future health status. In 2009, the Nutrition and Immunity Task Force of the International Life Sciences Institute, European Branch, organized an expert group to attempt to identify robust and predictive markers, or patterns or clusters of markers, which can be used to assess inflammation in human nutrition studies in the general population. Inflammation is a normal process and there are a number of cells and mediators involved. These markers are involved in, or are produced as a result of, the inflammatory process irrespective of its trigger and its location and are common to all inflammatory situations. Currently, there is no consensus as to which markers of inflammation best represent low-grade inflammation or differentiate between acute and chronic inflammation or between the various phases of inflammatory responses. There are a number of modifying factors that affect the concentration of an inflammatory marker at a given time, including age, diet and body fatness, among others. Measuring the concentration of inflammatory markers in the bloodstream under basal conditions is probably less informative compared with data related to the concentration change in response to a challenge. A number of inflammatory challenges have been described. However, many of these challenges are poorly standardised. Patterns and clusters may be important as robust biomarkers of inflammation. Therefore, it is likely that a combination of multiple inflammatory markers and integrated readouts based upon kinetic analysis following defined challenges will be the most informative biomarker of inflammation.

Adherence to Mediterranean diet reduces the risk of metabolic syndrome: a 6-year prospective study.

BACKGROUND AND AIMS: Benefits of Mediterranean diet on MetS risk have been suggested, but overall prospective evidence in the general population is limited. For the first time, the prospective association of adherence to Mediterranean diet with the 6-y risk of MetS and its components was evaluated in a large cohort in Europe. METHODS AND RESULTS: Subjects included were participants from the Supplémentation en Vitamines et Minéraux AntioXydants (SU.VI.MAX) study. Adherence to Mediterranean diet was assessed using traditional Mediterranean diet score (MDS), an updated Mediterranean score (MED) and Mediterranean style-dietary pattern score (MSDPS) calculated from at least three 24-h records. In 3232 subjects, the association between Mediterranean diet scores and 6-y risk of MetS was evaluated. The association between Mediterranean scores and MetS components was also estimated. A lower risk of MetS was observed with increasing MED score (P-trend = 0.001) and MDS (P-trend = 0.03) in multivariate models. The adjusted odds ratios (95% Confidence Interval) for MetS risk were 0.47 (0.32-0.69) and 0.50 (0.32-0.77) in subjects in the highest versus lowest tertile of MED score and MDS, respectively. The MED score was inversely associated with waist circumference, systolic blood pressure and triglycerides, and directly associated with HDL-cholesterol. The MDS was negatively associated with waist circumference and triglycerides, and MSDPS was positively associated with HDL-cholesterol. CONCLUSIONS: All Mediterranean diet scores were associated in a potentially beneficial direction with components of MetS or MetS incidence. Our findings support that individuals should be encouraged to follow a Mediterranean dietary pattern for reduction of MetS risk.

Prevention of overweight in preschool children: results of kindergarten-based interventions.

OBJECTIVE: Given the increasing prevalence of pediatric obesity, we evaluated two kindergarten-based strategies for reducing overweight in preschool children in the Haute-Garonne Department in France. METHODS: Kindergartens (n=79) were randomly assigned to one of the two strategies and followed for 2 years. In the first group (Epidémiologie et prévention de l'obésité infantile, EPIPOI-1), parents and teachers received basic information on overweight and health, and children underwent screening to identify those with overweight (body mass index (BMI) > or = 90th percentile) or at risk for overweight (BMI between 75 and 90th percentile), who were then followed up by their physicians. EPIPOI-2 children, in addition, received kindergarten-based education to promote healthy practices related to nutrition, physical activity and sedentary behaviors. Data on control children from non-intervention kindergartens (n=40) were retrieved from medical records at the Division of School Health. RESULTS: At baseline, groups differed significantly on age and school area (underprivileged/not). Owing to a significant interaction between school area and group, analyses were stratified by school area. At baseline, groups did not differ on overweight prevalence and BMI z-scores for any school area. After intervention, prevalence of overweight, BMI z-score and change in BMI z-score were significantly lower in intervention groups compared with controls in underprivileged areas. Using multilevel analysis adjusted for potential confounders, a significant effect on overweight prevalence at the end of the study was noted for EPIPOI-1 in underprivileged areas only (odds ratio and 95% confidence interval: 0.18 (0.07-0.51). In non-underprivileged areas, the gain in BMI z-score was lower in EPIPOI-2 group compared with control and EPIPOI-1. CONCLUSION: Our results suggest that simple measures involving increasing awareness on overweight and health, and periodic monitoring of weight and height with follow-up care when indicated, could be useful to reduce overweight in young children from underprivileged areas. A reinforced strategy with an education component, in addition, may be indicated in children in non-underprivileged areas.

Socioeconomic position, macroeconomic environment and overweight among adolescents in 35 countries.

OBJECTIVE: It is important to understand levels and social inequalities in childhood overweight within and between countries. This study examined prevalence and social inequality in adolescent overweight in 35 countries, and associations with macroeconomic factors. DESIGN: International cross-sectional survey in national samples of schools. SUBJECTS: A total of 11-, 13- and 15-year-olds from 35 countries in Europe and North America in 2001-2002 (N=162 305). MEASUREMENTS: The main outcome measure was overweight based on self-reported height and weight (body mass index cut-points corresponding to body mass index of 25 kg/m(2) at the age of 18 years). Measures included family and school affluence (within countries), and average country income and economic inequality (between countries). RESULTS: There were large variations in adolescent overweight, from 3.5% in Lithuanian girls to 31.7% in boys from Malta. Prevalence of overweight was higher among children from less affluent families in 21 of 24 Western and 5 of 10 Central European countries. However, children from more affluent families were at higher risk of overweight in Croatia, Estonia and Latvia. In Poland, Lithuania, Macedonia and Finland, girls from less affluent families were more overweight whereas the opposite was found for boys. Average country income was associated with prevalence and inequality in overweight when considering all countries together. However, economic inequality as measured by the Gini coefficient was differentially associated with prevalence and socioeconomic inequality in overweight among the 23-high income and 10-middle income countries, with a positive relationship among the high income countries and a negative association among the middle income countries. CONCLUSION: The direction and magnitude of social inequality in adolescent overweight shows large international variation, with negative social gradients in most countries, but positive social gradients, especially for boys, in some Central European countries. Macroeconomic factors are associated with the heterogeneity in prevalence and social inequality of adolescent overweight.

Association of macronutrient intake patterns with being overweight in a population-based random sample of men in France.

AIM: Diet is considered an important modifiable factor in the overweight. The role of macronutrients in obesity has been examined in general in selected populations, but the results of these studies are mixed, depending on the potential confounders and adjustments for other macronutrients. For this reason, we examined the association between macronutrient intake patterns and being overweight in a population-based representative sample of middle-aged (55.1+/-6.1 years) men (n=966), using various adjustment modalities. METHODS: The study subjects kept 3-day food-intake records, and the standard cardiovascular risk factors were assessed. Weight, height and waist circumference (WC) were also measured. RESULTS: Carbohydrate intake was negatively associated and fat intake was positively associated with body mass index (BMI) and WC in regression models adjusted for energy intake and other factors, including age, smoking and physical activity. However, with mutual adjustments for other energy-yielding nutrients, the negative association of carbohydrate intake with WC remained significant, whereas the associations between fat intake and measures of obesity did not. Adjusted odds ratios (95% confidence interval) comparing the highest and lowest quartiles of carbohydrate intake were 0.50 (0.25-0.97) for obesity (BMI>29.9) and 0.41 (0.23-0.73) for abdominal obesity (WC>101.9 cm). CONCLUSION: Consistent negative associations between carbohydrate intake and BMI and WC were seen in this random representative sample of the general male population. The associations between fat intake and these measures of being overweight were attenuated on adjusting for carbohydrate intake. Thus, the balance of carbohydrate-to-fat intake is an important element in obesity in a general male population, and should be highlighted in dietary guidelines.

Metabolic syndrome is associated with markers of subclinical atherosclerosis in a French population-based sample.

Metabolic syndrome (MetS) is associated with increased risk of cardiovascular disease (CVD). The relation of MetS with early stages of atherosclerosis, more important from a prevention perspective, has not been evaluated extensively. We examined the association of MetS, using WHO and NCEP definitions, with number of carotid and femoral plaques; carotid intima-media thickness (IMT); pulse wave velocity (PWV) in a random population-based sample of 1153 French adults (35-65 year). Impact of inflammatory factors (C-reactive protein and soluble intercellular adhesion molecule-1) on these parameters was also evaluated. Prevalence of MetS was 14.5 (CI: 12.3-16.0) and 17.5 (CI: 15.1-20.2)%, using NCEP and WHO definitions, respectively. MetS significantly predicted number of plaques, IMT, and PWV after adjustment for traditional risk factors (P<0.05). Inflammatory factors predicted peripheral plaques only. The risk of subclinical atherosclerosis was considerably increased with MetS (P<0.05); odds ratios ranged 1.80-2.15 with NCEP definition, and 1.48-1.97 with WHO definition. Individuals meeting both NCEP and WHO definitions had slightly greater risk of increased plaques, IMT, and PWV. MetS was strongly associated with subclinical atherosclerosis and aortic stiffness, and can be used as a surrogate marker for high CVD risk, deserving aggressive treatment.

Doege-Potter Syndrome.

Doege-Potter syndrome is a rare paraneoplastic syndrome presenting as a hypoinsulinaemic hypoglycaemia from the ectopic secretion of a prohormone of insulin-like growth factor II (IGF-II) from a solitary fibrous tumour. Surgical resection is curative in the majority of cases. If, however, the diagnosis is not suspected and treatment is delayed, it can lead to hypoxic cerebral injury or death. The underlying tumour can be a benign or malignant pleural tumour but may be present in extrapleural sites. For a diagnosis of Doege-Potter syndrome, symptoms attributable to hypoglycaemia and low blood glucose levels should be present along with the secretion of prohormone IGF-II. We report a case of severe hypoglycaemia in a 76-year-old inpatient admitted for resection of a recurrent left-sided pleural tumour. Investigation revealed true hypoglycaemia and Doege-Potter syndrome was diagnosed. The tumour was completely resected and the patient made a full recovery with no further hypoglycaemic episodes.

Cloning and expression of a chicken alpha-amylase gene.

We have isolated and sequenced a genomic clone for a pancreatic alpha-amylase gene (amy) of the chicken (Gallus gallus). The gene is interrupted by nine introns, spans over 4 kb, and encodes a protein (AMY) of 512 aa that is 83% identical to the human pancreatic alpha-amylase enzyme. Southern blot analysis of chicken DNA revealed two distinct pancreatic amy loci. In addition, we have generated a cDNA from chicken pancreatic RNA corresponding to the coding sequence of the genomic clone. The cDNA was inserted into a yeast expression vector, and the resulting construct used to transform Saccharomyces cerevisiae cells. Transformed yeast cells synthesized and secreted active AMY enzyme, and the gel migration pattern of the alpha-amylase produced by the yeast cells was identical to that of the native chicken enzyme.

Spot ferritin assay for serum samples dried on filter paper.

A spot method was developed for analyzing ferritin from 20-microL serum samples (n = 71) that were spotted and dried on filter paper and stored frozen (2 d). Spot samples were thawed, incubated in a buffer containing cellulase, and centrifuged and the supernate assayed for ferritin by a commercial radioimmunoassay. The geometric means (+/- 1 SD) for ferritin analyzed with the spot and traditional methods were 49.4 (range: 14.9-164.0) and 47.5 (range: 14.4-156.0) micrograms/L, respectively. The two methods correlated strongly (r = 0.98, P = 0.0001). Storage of spot samples (n = 31) under various conditions (at room temperature, refrigerated, or frozen for 2 wk, or at room temperature for 4 wk) in airtight bags before analysis yielded ferritin values that were not significantly different from those obtained by the traditional method. Ferritin values from spotted samples stored at room temperature for 4 wk before being analyzed were only 2.2 micrograms/L higher than those from samples analyzed by the traditional method. With iron depletion defined as a serum ferritin concentration < 15 micrograms/L, this method corresponded absolutely with the traditional method in classifying individuals as iron sufficient or deficient. Thus, the spot ferritin method (with samples stored at room temperature for 4 wk) offers a reliable, accurate, and practical tool for iron status assessment in field studies. Capillary blood can be sampled to avoid the costs and concerns associated with venipuncture and spotted serum samples can be stored at room temperature for > or = 4 wk, eliminating the need for freezing during storage and transportation.

Day-to-day variation in iron-status indexes in elderly women.

Day-to-day variability in biochemical indicators of iron status in well-hydrated and healthy women 70-79 y old (n = 10) was determined. Venous blood was collected on 4 nonconsecutive days during a 2-wk period. Analytical (sigma 2 rep) and biological (sigma 2 fd) variance components were computed based on a previously established scheme in younger adults. These two variance components were summed to obtain the total day-to-day variability (sigma 2 fd). Our results indicate that biological variation contributed most to the intraindividual variation. We calculated that sampling once for most iron indexes and twice for plasma transferrin receptors in elderly individuals is adequate to accurately determine these indexes whereas serum iron and transferrin saturation, indexes with high CVfd, require seven and eight measurements, respectively. These data, compared with previously published data in younger adults, demonstrate that aging is associated with a decreased variation in some indexes of iron status such as serum ferritin.

Iron deficiency and anemia of chronic disease in elderly women: a discriminant-analysis approach for differentiation.

To differentiate iron-deficiency anemia and anemia associated with chronic inflammatory diseases in elderly women, subsets of laboratory, dietary, and functional assessment variables were obtained by using discriminant analysis. Fifty-one subjects (70-79 y of age) were classified into one of four groups on the basis of the presence of iron deficiency and chronic inflammatory disease. Iron deficiency was defined on the basis of a significant response in hemoglobin concentration after iron supplementation. The discriminating subset of laboratory tests consisted of measures for serum ferritin, plasma transferrin receptors, and erythrocyte sedimentation rate. The discriminant function classified subjects into iron-deficient, anemia of chronic disease, or a category in which the two coexist, with an error rate of 18.6%. The addition of other variables (dietary iron and functional assessment information) did not appreciably improve the classification. The results of these three key laboratory tests may help to identify functional iron deficiency in the presence of chronic inflammation.

Evaluation of a gastric delivery system for iron supplementation in pregnancy.

The present investigation was undertaken to assess the efficacy of oral iron supplementation during pregnancy by using a gastric delivery system (GDS). Three hundred seventy-six pregnant women between 16 and 35 y of age and 14 and 22 wk gestation were selected if mild anemia was present (hemoglobin concentration 80-110 g/L). The participants were randomly assigned to one of three study groups given no iron, two FeSO4 tablets (100 mg Fe) daily, or one GDS capsule (50 mg Fe) daily. Blood was obtained initially and after 6 and 12 wk for measurement of red blood cell and iron indexes, including serum transferrin receptor. There was a significant and comparable improvement in hematologic and iron-status measurements in the two groups of women given iron whereas iron deficiency evolved in women given no iron supplement. We conclude that by eliminating gastrointestinal side effects and reducing the administration frequency of an iron supplement to once daily, a GDS offers significant advantages for iron supplementation of pregnant women.

Immune function did not decline with aging in apparently healthy, well-nourished women.

Nutrition plays a crucial role in immune function. Most studies on age-associated changes in immunocompetence in healthy adults did not examine the nutritional status of participants extensively. Inadequate nutritional status may confound the relationship of aging and immune response. The purpose of this study was to examine age-related changes in parameters of acquired and innate immunity in healthy and generally well-nourished older (62-88 years) versus younger (20-40 years) women. Subjects were screened for participation using the health criteria of the SENIEUR protocol as well as a number of nutrition criteria related to undernutrition, and protein, iron, vitamin B12, and folate status. Young and old women did not differ in total T (CD3+), T-helper (CD4+), or T-cytotoxic (CD8+) cell number. However, older women tended to have lower T-cell proliferation response to concanavalin A (P < 0.10) and significantly reduced response to phytohemagglutinin (P < 0.05). No age-related changes were noted in natural killer cell number or cytotoxicity. Phagocytosis and subsequent oxidative burst activity also did not differ between young and old women. Most immune parameters were not compromised with aging in this cohort of apparently healthy, well-nourished women. These findings highlight the importance of simultaneous examination of health and nutritional status in studies of immune function with aging.

Cytokine production by stimulated mononuclear cells did not change with aging in apparently healthy, well-nourished women.

Aging is often associated with a dysregulation of the immune system. We examined mitogen-stimulated production of interleukin (IL)-2 and proinflammatory cytokines, IL-1beta and IL-6, in apparently healthy and generally well-nourished old versus young women. Subjects were screened for health using the SENIEUR protocol and a panel of laboratory tests for inflammation, as well as for the adequacy of nutritional status using criteria related to undernutrition, and protein, iron, vitamin B(12), and folate status. Young (n=26, age: 20-40 years) and old (n=44, age: 62-88 years) cohorts did not differ on the number of circulating monocytes, granulocytes, B (CD19+) cells, and T (CD3+, CD4+, and CD8+) cells. No differences (P>0.10) were seen between the two age groups in IL-2, IL-1beta and IL-6 levels in whole blood cultures at 48 h after stimulation with PHA (5 mg/l). Furthermore, no age-related differences were noted in the absolute amounts (pg) of IL-1beta and IL-6 after normalizing for circulating monocytes, B cells, or T cells (P>0.10). Similarly, no age-related decline in absolute amount of IL-2 (pg) after normalizing for circulating T cells was noted (P>0.10). Thus, contrary to most previous reports, our results do not support an increase in the production of proinflammatory cytokines IL-1beta and IL-6, and a reduced production of IL-2 with aging when health and nutritional status are maintained. These findings support our previous results of no change in monocyte function and few alterations in acquired immune response in a carefully selected group of healthy and well-nourished elderly women.

Diagnostic utility of serum transferrin receptors measurement in assessing iron status.

Serum transferrin receptors (TfR) are a sensitive index of tissue iron availability, increasing progressively in response to functional iron deficiency. Unlike conventional laboratory tests of iron status, serum TfR are unaffected by underlying acute or chronic infection. Therefore, serum TfR measurement is particularly promising for evaluation of iron status when iron deficiency is simultaneously present with overt or subclinical infection or inflammation--a scenario often seen in patients seeking medical care, in elderly persons, and in persons living in developing countries. This test is also promising for assessment of iron status in pregnancy because it is not confounded by gestational effects. With the exception of conditions associated with markedly enhanced erythropoiesis which can increase TfR independently (e.g., megaloblastic anemia, thalassemia), serum TfR determination is a specific test of iron status. Serum TfR measurement is also reliable; a single, small amount of blood sample is adequate for its accurate determination. These sensitivity, specificity, and reliability characteristics of serum TfR measurement enable it to enhance confidence in iron status assessment in complex situations with the standard repertoire of laboratory tests.

Evaluation of gastric antral motor performance in patients with dysmotility-like dyspepsia using real-time high-resolution ultrasound.

Although manometric antral hypomotility and delayed gastric emptying have been reported separately in patients with dyspepsia, relationships between symptoms, antral contractility and emptying rate have not been sought. The present study therefore aimed to evaluate, simultaneously, gastric antral excursion characteristics and emptying in a sub-group of patients with severe functional dyspepsia using high-resolution real-time ultrasound. The circumference of the relaxed and contracted antrum was measured at 15-min intervals after ingestion of a 360 mL mixed nutrient meal in 36 chronic dyspepsia patients with symptoms of post-prandial bloating and epigastric distension, and in 25 healthy volunteers. Antral emptying (measured as the rate of decrease in circumference of the relaxed antrum) was slower in patients than normals (P = 0.02). In both groups, the average values for antral excursion were similar but the range of excursion in patients was significantly wider than in controls (F < 0.001), with 11 patients showing values above, and 8 showing values below the normal range. There was no relationship between antral emptying and antral excursion in either patients or volunteers. In conclusion, patients with severe functional dyspepsia show a wide range of antral performance characteristics, suggesting not only that the mechanisms responsible for the control of antral motor function are disturbed but also that the cause of the symptoms and the disturbed antral motor function are probably not directly related.

CLO vs histology: optimal numbers and site of gastric biopsies to diagnose Helicobacter pylori.

OBJECTIVE: To determine the optimal numbers and sites of biopsies required for diagnosis of Helicobacter pylori by using the CLOtest and comparing the results with those of a routine histological assessment in a district general hospital (DGH) setting. METHODS: A prospective study comparing the sensitivity of the CLOtest containing one antral (CLO 1), two antral (CLO 2) and two antral and one body biopsy (CLO 3), and with histological examination for H. pylori. Consecutive patients undergoing upper gastrointestinal endoscopy (UGIE) at Stepping Hill Hospital, Stockport, UK, who had evidence of gastritis, gastric ulcer, duodenitis or duodenal ulcer were included in the study. RESULTS: Ninety-six patients were biopsied. Forty were positive on at least one of the CLOtests; of these, nine were negative on histological assessment. Of these nine, two were positive on all CLOtests and seven were positive only on CLO 3. One was positive on histology but negative on all CLOtests. This study showed that CLO 3 was more sensitive than CLO 1 (P = 0.004), CLO 2 (P = 0.016) and histology (P = 0.022). There was no significant difference between CLO 1 and CLO 2 (P = 0.500), CLO 1 and histology (P = 1.000), CLO 2 and histology (P = 1.00). CONCLUSION: We feel that in a busy clinical setting, taking two antral and one body biopsy in a single CLOtest is superior to routine histological assessment for the detection of H. pylori, with resulting cost saving.

Day-to-day variation in iron status indexes is similar for most measures in elderly women with and without rheumatoid arthritis.

OBJECTIVE: To determine the day-to-day variation in biochemical measures of iron status in a group of elderly women with rheumatoid arthritis compared with a group of healthy elderly women. DESIGN: Venous blood samples were collected from each subject on 3 nonconsecutive days during a 2-week study period; subjects had fasted overnight. Variability in hemoglobin level, hematocrit value, serum iron concentration, total iron-binding capacity, transferrin saturation, serum ferritin concentration, and plasma transferrin receptor level was determined. SUBJECTS: Two groups of women, one with rheumatoid arthritis (n=10) and another that was apparently healthy (n=10). STATISTICAL ANALYSES: Variance component analysis was used to estimate the biological variation (sigma square day) and analytic variation (sigma square rep) for each iron index. The coefficient of variation (CV) for each variance component was calculated: coefficient of biological variation = CV day, coefficient of analytic variation = CV rep, and coefficient of a single future determination = CV fd. RESULTS: The CV rep for all iron indexes was smaller than the CV day in both groups. The CV day was considerably higher for serum iron concentration and for transferrin saturation than for the other indexes in both groups (16.6% and 16.6% in healthy subjects and 33.6% and 28.2%, respectively, in subjects with rheumatoid arthritis). The higher CV day for serum iron concentration and transferrin saturation translated into a higher CV fd for these indexes. Because of the higher variance for these two indexes, more sampling days were required for reliable estimates. CV day and CV fd for plasma transferrin receptor level were relatively low. CONCLUSIONS: These findings corroborate our previous finding that variation of serum ferritin concentration in the elderly is lower than that demonstrated in younger populations. This aging effect persists in the presence of rheumatoid arthritis. Fasting appeared to improve reliability in the determinations for serum iron concentration and transferrin saturation. Variability estimates for the indexes other than serum iron concentration and transferrin saturation were not altered by the inflammation of rheumatoid arthritis. Plasma transferrin receptor level is a reliable index for assessing iron status in populations with rheumatoid arthritis.