Patatin-like phospholipase 3 (rs738409) gene polymorphism is associated with increased liver enzymes in obese adolescents and metabolic syndrome in all ages.

BACKGROUND: Obesity is associated with non-alcoholic fatty liver disease (NAFLD), and the patatin-like phospholipase 3 (PNPLA3) rs738409 (Ile148Met, C>G) gene polymorphism is one of the most important genetic determinants of NAFLD. Carriers have been reported to better respond to lifestyle modification. AIM: To investigate the effect of rs738409 on overweight/obese adolescents and adults with and without metabolic syndrome (MetS). METHODS: Two hundred and eighty-eight overweight/obese and 209 normal weight participants of the STYJOBS/EDECTA cohort (NCT00482924) were analysed for PNPLA3 genotypes. RESULTS: Compared to overweight/obese without MetS, in overweight/obese study participants with MetS, the presence of the G allele (148Met) was significantly higher (CC: 5.0% vs. 9.2%, Spearman's correlation, 0.12; P = 0.038). Persons with CG (heterozygote for the risk allele) and with GG (homozygote for the risk allele) genotypes showed significantly higher ALT levels than those with CC genotypes. Even young individuals aged below 20 years had significantly increased ALT levels if they were homozygote with the G allele. CONCLUSIONS: The PNPLA3 rs738409 polymorphism is associated already in youths with increased ALT, and is more frequent in obese with MetS of all ages. Hence, overweight/obese rs738409 carriers should be identified early in life and treated with a rigorous life style intervention.

Primary epiploic appendagitis and fructose malabsorption.

Primary epiploic appendagitis (PEA) is a rare cause of abdominal acute or subacute complaints. Diagnosis of PEA is made when computed tomography (CT) reveals a characteristic lesion. We report on contrast-enhanced CT images of a patient with PEA and regression of inflammation and the reduction in size of the inflamed appendage over the time period of 4 months. Patients with PEA usually recover without medication or surgical treatment within a few weeks. However, due to continuing bloating and irregular bowel movements we investigated carbohydrate malabsorption and diagnosed a fructose malabsorption. Bloating and irregular bowel movements in this patient with PEA were correlated to carbohydrate malabsorption and were treated successfully with a diet free of culprit carbohydrates.

Antioxidant food supplements and obesity-related inflammation.

The obesity prevalence is growing worldwide and largely responsible for the increased incidence of cardiovascular disease, the most common cause of death in the western world. Excessive food intake along with insufficient physical exercise is the basic impetus for this development. The obese state is commonly associated with an increase in leptin levels and chronic immune-mediated inflammation. Despite high leptin levels, the leptin response, normally associated with satiety and satiation, seems to be impaired and individuals continue to consume calorie-rich food. Antioxidant food additives such as sodium sulphite, sodium benzoate and curcumin were shown to suppress the leptin release in lipopolysaccharide- treated murine adipocytes. Based on this, we hypothesize that the insufficient leptin release, caused by excessive consumption of food additives, may lead to a reduced exposure of the central nervous system to leptin and ultimately propagate obesity. On the other hand, leptin has been shown to favor Th1-type activity, which ultimately decreases tryptophan levels. Tryptophan derivatives, serotonin and melatonin, induce satiety/satiation through several mechanisms. In this context, the antioxidant suppression of leptin release and Th1-type activity is beneficial to increase serotonin and melatonin levels. The molecules in the mechanism described in this review are highly integrated in the reward system, and have been implicated in the addiction behavior of obesity. Based on these facts, the involvement of antioxidant food supplements in the mechanisms of the reward-deficiency syndrome which perpetuates obesity will be discussed.

High risk vs. "metabolically healthy" phenotype in juvenile obesity - neck subcutaneous adipose tissue and serum uric acid are clinically relevant.

BACKGROUND: Since obesity and its associated co-morbidities do not only have effect on the individual patient, but also on society and the health system, it is of great importance to investigate this lifestyle-disease. The rationale of this study was to distinguish metabolically healthy from unhealthy overweight/obese patients as compared to healthy normal weight children and adolescents by means of a comprehensive anthropometric, laboratory and sonomorphological vascular assessment. MATERIALS AND METHODS: 299 study participants were derived from the prospective, observational study STYJOBS/EDECTA (STYrian Juvenile Obesity Study/Early DEteCTion of Arteriosclerosis). Standard anthropometric data were obtained for each subject. This study comprised different diagnostic steps: extended anthropometry (Lipometer®), carotid artery ultrasound, various laboratory measurements, blood pressure measurement, oral glucose tolerance test. Ow/ob juveniles were classified as "metabolically healthy" (no laboratory criteria of metabolic syndrome fulfilled) vs. "metabolically unhealthy" (≥ 3 criteria of metabolic syndrome). Results underwent statistical evaluation, including t-test or Mann-Whitney U-test, regression analysis and a p-value < 0.05 was considered statistically significant. RESULTS AND DISCUSSION: In the study's central European cohort only about 16% (n=48/299) of the overweight/obese juveniles can be regarded as metabolically healthy. About 36% (n=108/299) of the overweight/obese patients fulfilled the criteria for metabolic syndrome. High visceral fat stores (p<0.001) and their clinical surrogate waist circumference (p<0.001) determine an adverse metabolic phenotype. Several parameters, including uric acid (p<0.001), adiponectin (p<0.05), insulin resistance (HOMA-Index, p<0.001), nuchal SAT thickness (p<0.001), arteriosclerosis of the carotids (p<0.001), and others are responsible for the distinction between -metabolically healthy and unhealthy juveniles. Nevertheless, "healthy obesity" only defines a sub-phenotype of a disease effecting rising numbers of young patients. CONCLUSIONS: Since obesity in children and adolescents is not a consistent entity, it remains crucial to differ between metabolically healthy and unhealthy obese children in order to achieve appropriate intervention and prevention for our patients.

Blurred vision and myopic shift in Puumala virus infections are independent of disease severity.

Puumala virus infection causes epidemic nephropathia (NE), a certain type of haemorrhagic fever with renal syndrome (HFRS). Myopic shift is considered a pathognomonic sign of NE and HFRS but rates of ocular involvement vary. The aim of the study was to evaluate whether clinical and laboratory findings are associated with ophthalmic involvement in NE in Austria. We found that blurred vision and myopic shift are frequent in Puumala virus infections in Austria but are independent of disease severity.

Epidemiology of invasive fungal infections and rationale for antifungal therapy in patients with haematological malignancies.

Invasive fungal infections (IFIs) in patients with haematological malignancies are difficult to diagnose and outcome is often fatal. Over the 7-month study period, 117 cases with haematological malignancies receiving systemic antifungal treatment were included. Data regarding antifungal agents, dosage and reason for administration were recorded. Fungal infections in study patients were classified as possible, probable or proven according to recent European Organization for Research and Treatment of Cancer criteria. During the study period, 690 cases with haematological malignancies were admitted. A total of 117 cases received systemic antifungal therapy. Twenty-four of 117 patients (21%) had possible, six (5.1%) had probable and four (3.4%) had proven IFI. Seven of 10 probable and proven infections were caused by Candida spp., 2 by Aspergillus spp. and 1 by a fungus belonging to Zygomycetes. Fifty-two of 117 patients (44%) received antifungal prophylaxis, 81 of 117 (69%) received empirical (31/117; 26%) or pre-emptive (50/117; 43%) antifungal therapy and four of 117 patients (3.4%) directed antifungal therapy. Mostly, systemic antifungal therapy was administered empirically or pre-emptively. Twenty-nine per cent of cases receiving systemic antifungal treatment met the international consensus criteria of mostly possible IFI, whereas 71% did not. Proven invasive fungal infections were rare.

Somatostatin receptor scintigraphy in patients with cat-scratch disease.

AIM: Somatostatin receptor scintigraphy images various neoplastic, granulomatous, and auto-immune diseases. Cat-scratch disease in an infectious granulomatous disease usually affecting the lymphnodes. It is not known whether cat-scratch disease provides positive somatostatin receptor scintigrams. PATIENTS, METHODS: Twelve patients with lymphadenitis and suspected cat-scratch disease were investigated by immunofluorescence antibody testing and somatostatin receptor scintigraphy. Suppurated lymphnodes were extracted or drained and Bartonella henselae specific PCR was then performed. RESULTS: Eleven of 12 patients showed IgG antibodies against B. henselae. SRS showed positive scintigraphic results in 6 of 11 patients with CSD. B. henselae DNA was detected in tissue of lymphnodes from 4 of 5 patients with lymphnode extraction or lymphnode drainage. SRS demonstrated positive scintigrams in all patients with a positive PCR. In one patient with suspected CSD SRS was negative as well as antibody testing. CONCLUSION: Somatostatin receptor scintigraphy correlated with positive Bartonella henselae specific PCR tests and positive Bartonella henselae specific antibody tests in patients with CSD.

Body fat distribution of overweight females with a history of weight cycling.

Weight cycling may cause a redistribution of body fat to the upper body fat compartments. We investigated the distribution of subcutaneous adipose tissue (SAT) in 30 overweight women with a history of weight-cycling and age-matched controls (167 normal weight and 97 overweight subjects). Measurements of SAT were performed using an optical device, the Lipometer. The SAT topography describes the thicknesses of SAT layers at 15 anatomically well-defined body sites from neck to calf. The overweight women with a history of weight cycling had significantly thicker SAT layers on the upper body compared to the overweight controls, but even thinner SAT layers on their legs than the normal weight women. An android fat pattern was attributed to overweight females and, even more pronounced, to the weight cyclers. The majority of normal weight women showed a gynoid fat pattern. Using stepwise discriminant analysis, 89.0% of all weight cyclers and overweight controls could be classified correctly into the two groups. These findings show the importance of normal weight maintenance as a health-promoting factor.

Silent haemoglobin variants and determination of HbA(1c) with the HPLC Bio-Rad Variant II.

AIMS: To evaluate the determination of HbA(1c) with an automated high performance liquid chromatography (HPLC) method in patients with clinically silent haemoglobin variants. METHODS: HbA(1c) values were determined with the ion exchange HPL Bio-Rad Variant II using the high resolution beta thalassaemia programme in patients with silent haemoglobin variants, namely: Hb Graz, Hb Sherwood Forest, Hb O Padova, and Hb D. RESULTS: All of these haemoglobin variants caused additional peaks in the chromatograms. No clinically useful HbA(1c) results were produced for patients with Hb Graz and Hb Sherwood Forest, the results for the patient with Hb D were too low, but the results for patients with Hb O Padova were acceptable. CONCLUSIONS: The development of this automated HPLC method modification with high resolution mode aids the identification of interference caused by the described clinically silent haemoglobin variants in HbA(1c) determination.

Recurrent septicemia due to Campylobacter fetus and Campylobacter lari in an immunocompetent patient.

We describe a severe and recurrent septicemia due to Campylobacter in a 75-year-old immunocompetent patient. Two Campylobacter strains were detected in several blood cultures. Campylobacter fetus and Campylobacter lari were identified with PCR tests based on species-specific nucleotide sequences for the 16S rRNA gene.

Oxidative stress during peripheral angioplasty. Implication for late restenosis?

BACKGROUND: Percutaneous transluminal angioplasty (PTA) is routine treatment for patients with peripheral arterial disease (PAD). The procedure induces local generation of reactive oxygen species (ROS), such as H2O2. Since these have been shown to stimulate vascular smooth muscle cell growth (VSMCG), we investigated peroxide levels in patients with PAD during PTA and related these results to late clinical outcome. METHODS: Thirty patients (17 male, 13 female, 20 Fontain stage II, 10 Fontaine stage IV, median age 68 years) undergoing PTA of a 2-6 cm stenosis of the femoral or popliteal artery were included. The procedure was performed successfully in all patients. At follow-up six months thereafter restenosis was evaluated by duplex sonography. Total peroxide concentrations were determined in plasma drawn before, 6, 24 and 48 hours after the procedure by the Operoxide activityO assay, which is based on the reaction of horseradish peroxidase with plasma peroxides, using tetramethylbenzidine as the chromogenic substrate. RESULTS: The median peroxide level before angioplasty was 280 mmol/L (range 47-549). Levels were higher in patients with advanced disease, in smokers and in patients with diabetes. In response to angioplasty, peroxide levels increased within 48 hours (p<0.001). Six months after the procedure, restenosis was observed in 10/30 (33 percent) of patients. Clinical outcome was not dependent upon baseline or postinterventional peroxide levels. CONCLUSIONS: Elevated peroxide levels are seen in patients with advanced arteriosclerotic disease and in those with diabetes, but are not predictive for late restenosis.

Microdissection and reverse painting reveals a microdeletion 6(q26qter) in a de novo r(6) chromosome.

Ring chromosomes 6 are rare constitutional abnormalities with inconsistent phenotypic and clinical features. One of the reasons for this variability is the cytogenetically undetectable loss of chromosomal material from the telomeric segments at 6p or 6q. We have therefore used fluorescence in situ hybridization (FISH) to analyse a ring chromosome 6 that was detected in a newborn boy with dysmorphic features. Reverse painting of the microdissected ring chromosome onto normal metaphase spreads revealed a small deletion of the terminal region of the long arm, 6(q26qter). Moreover, the simple all-telomeric sequence (TTAGG)n was lost, whereas the p-specific subtelomeric sequence was still present. Our findings confirm that microdeletions occur during the formation of r(6) chromosomes and, therefore, are an important determinator of the associated phenotype.

Hemoglobin variants and determination of glycated hemoglobin (HbA1c).

Measurement of glycated hemoglobin in diabetic patients is an established procedure for evaluating long-term control of diabetes. The Diabetes Control and Complications Trial (DCCT), as well as the United Kingdom Prospective Diabetes Study (UKPDS), confirmed the direct relationship between the degree of glycemic control as estimated by glycohemoglobin (GHb) determinations and the development and progression of long-term complications in diabetic patients. Samples with known interferences of HbA(1c) determination as hemoglobinopathies are specifically excluded from certification testing and there are no guidelines or requirements for comparability of samples containing hemoglobin (Hb) variants. This paper reviews the interference of Hb variants on determination methods of glycated hemoglobin as they result in false HbA(1c) results.