Ranges of phenotypic flexibility in healthy subjects.

BACKGROUND: A key feature of metabolic health is the ability to adapt upon dietary perturbations. A systemic review defined an optimal nutritional challenge test, the "PhenFlex test" (PFT). Recently, it has been shown that the PFT enables the quantification of all relevant metabolic processes involved in maintaining or regaining homeostasis of metabolic health. Furthermore, it was demonstrated that quantification of PFT response was more sensitive as compared to fasting markers in demonstrating reduced phenotypic flexibility in metabolically impaired type 2 diabetes subjects. METHODS: This study aims to demonstrate that quantification of PFT response can discriminate between different states of health within the healthy range of the population. Therefore, 100 healthy subjects were enrolled (50 males, 50 females) ranging in age (young, middle, old) and body fat percentage (low, medium, high), assuming variation in phenotypic flexibility. Biomarkers were selected to quantify main processes which characterize phenotypic flexibility in response to PFT: flexibility in glucose, lipid, amino acid and vitamin metabolism, and metabolic stress. Individual phenotypic flexibility was visualized using the "health space" by representing the four processes on the health space axes. By quantifying and presenting the study subjects in this space, individual phenotypic flexibility was visualized. RESULTS: Using the "health space" visualization, differences between groups as well as within groups from the healthy range of the population can be easily and intuitively assessed. The health space showed a different adaptation to the metabolic PhenFlex test in the extremes of the recruited population; persons of young age with low to normal fat percentage had a markedly different position in the health space as compared to persons from old age with normal to high fat percentage. CONCLUSION: The results of the metabolic PhenFlex test in conjunction with the health space reliably assessed health on an individual basis. This quantification can be used in the future for personalized health quantification and advice.

Nutrigenomics approach elucidates health-promoting effects of high vegetable intake in lean and obese men.

We aimed to explore whether vegetable consumption according to guidelines has beneficial health effects determined with classical biomarkers and nutrigenomics technologies. Fifteen lean (age 36 ± 7 years; BMI 23.4 ± 1.7 kg m(-2)) and 17 obese (age 40 ± 6 years; BMI 30.3 ± 2.4 kg m(-2)) men consumed 50- or 200-g vegetables for 4 weeks in a randomized, crossover trial. Afterward, all subjects underwent 4 weeks of energy restriction (60 % of normal energy intake). Despite the limited weight loss of 1.7 ± 2.4 kg for the lean and 2.1 ± 1.9 kg for the obese due to energy restriction, beneficial health effects were found, including lower total cholesterol, LDL cholesterol and HbA1c concentrations. The high vegetable intake resulted in increased levels of plasma amino acid metabolites, decreased levels of 9-HODE and prostaglandin D3 and decreased levels of ASAT and ALP compared to low vegetable intake. Adipose tissue gene expression changes in response to vegetable intake were identified, and sets of selected genes were submitted to network analysis. The network of inflammation genes illustrated a central role for NFkB in (adipose tissue) modulation of inflammation by increased vegetable intake, in lean as well as obese subjects. In obese subjects, high vegetable intake also resulted in changes related to energy metabolism, adhesion and inflammation. By inclusion of sensitive omics technologies and comparing the changes induced by high vegetable intake with changes induced by energy restriction, it has been shown that part of vegetables' health benefits are mediated by changes in energy metabolism, inflammatory processes and oxidative stress.

An analysis of the impact of previous laparoscopic hysterectomy experience on the learning curve for robotic hysterectomy.

To analyze and compare the safety and perioperative outcomes of newly trained robotic surgeons with previous laparoscopic hysterectomy experience (TLH Exp) and those without previous laparoscopic hysterectomy experience (Non-TLH Exp). The purpose is to determine the effect of previous advanced laparoscopic skills on the performance in robotic assisted laparoscopic surgery. We will also compare the perioperative outcomes between the total laparoscopic hysterectomies (TLH), and robotic assisted laparoscopic hysterectomies (RALH) of a single experienced (TLH Exp) robotic surgeon. The purpose is to determine benefits and/or risks, if any, of one approach over the other in the hands of an experienced laparoscopic surgeon. Prospective data were collected on the first consecutive series of RALH performed by (TLH Exp) and (Non-TLH Exp) surgeons, with perioperative outcomes and morbidity being evaluated. In addition, retrsopective data were collected on a consecutive series of patients in a TLH group and compared with the outcomes in the robotic group for benign hysterectomies by the same surgeon. The parameters that were analyzed for associations with these two groups were estimated blood loss (EBL), Hb drop, length of hospital stay (LOS), procedure time, pain medication use, and complications. The (TLH Exp) group had 64 patients, and the (Non-TLH Exp) group had 72 patients. When comparing patients in the (TLH Exp) group with patients in (Non-TLH Exp) group, the mean age was 44 and 45 (P = 0.8), mean BMI was 27.7 and 29.5 kg/m(2) (P = 0.2), mean procedure time was 121 and 174 min (P < 0.05), mean console time was 70 and 119 min (P < 0.05), mean EBL was 64 and 84 ml (P = 0.3), with a Hb drop 1.7 and 1.33 (P = 0.2), uterine weight was 192 and 205 gms (P = 0.7), and length of stay was 1.07 and 1.33 days (P = 0.2), respectively. The (TLH Exp) surgeons had a lower OR, procedure and console time, but a higher hemoglobin drop, with no difference in EBL. There were no operative deaths, or conversions in either group. Morbidity occurred in two patients (3 %) in each group, with no statistically significant difference between the groups. In the (TLH Exp) group it included a blood transfusion and a readmission for a postoperative ileus. In the (Non-TLH Exp), the complications included a blood transfusion and a return to the OR for a vaginal cuff dehiscence. When comparing a single (TLH Exp) surgeon's own TLH versus RALH, there were 64 RALH and 49 TLH cases. There was a statistically significant difference in the mean procedure time 121.1 versus 88.8 min (P < 0.05), mean Hb drop 1.7 versus 2.3 (P < 0.05), and mean EBL 64.2 versus 158 ml (P < 0.05), respectively. The RALH group had a longer procedure time, but lower Hb drop, and less estimated blood loss. There were no operative deaths, or conversions in either group. Morbidity occurred in 2 patients in the robotic group, and included one blood transfusion, and one postoperative ileus. There were no complications noted in the laparoscopic hysterectomy group. Previous advanced laparoscopic skills appear to only significantly impact the length of the procedure, but not other variables. Robotic surgery may level the playing field between the basic and advanced laparoscopic surgeon for robotic assisted laparoscopic hysterectomy. In comparing the outcomes of RALH versus TLH by a single surgeon, the robotic assistance appeared to lengthen the procedure time, but reduce the amount of blood loss. Robotic surgery may offer a benefit of reduced blood loss at the expense of longer operating time. Similar studies including different surgeons are needed to validate these points, and thereby determine the risk-benefit balance between the two approaches for benign simple hysterectomies.

Matrix correlations for high-dimensional data: the modified RV-coefficient.

MOTIVATION: Modern functional genomics generates high-dimensional datasets. It is often convenient to have a single simple number characterizing the relationship between pairs of such high-dimensional datasets in a comprehensive way. Matrix correlations are such numbers and are appealing since they can be interpreted in the same way as Pearson's correlations familiar to biologists. The high-dimensionality of functional genomics data is, however, problematic for existing matrix correlations. The motivation of this article is 2-fold: (i) we introduce the idea of matrix correlations to the bioinformatics community and (ii) we give an improvement of the most promising matrix correlation coefficient (the RV-coefficient) circumventing the problems of high-dimensional data. RESULTS: The modified RV-coefficient can be used in high-dimensional data analysis studies as an easy measure of common information of two datasets. This is shown by theoretical arguments, simulations and applications to two real-life examples from functional genomics, i.e. a transcriptomics and metabolomics example. AVAILABILITY: The Matlab m-files of the methods presented can be downloaded from http://www.bdagroup.nl.

Expression profiling of colon cancer cell lines and colon biopsies: towards a screening system for potential cancer-preventive compounds.

Interest in mechanisms of colon cancer prevention by food compounds is strong and research in this area is often performed with cultured colon cancer cells. In order to assess utility for screening of potential cancer-preventive (food) compounds, expression profiles of 14 human cell lines derived from colonic tissue were measured using cDNA microarrays with 4000 genes and compared with expression profiles in biopsies of human colon tumours and normal tissue. Differences and similarities in the gene expression profiles of the cell lines were analysed by clustering and principal component analysis (PCA). Cytoskeleton genes and immune response genes are two functional classes of genes that contributed to the differences between the cell lines. A subset of 72 colon cancer-specific genes was identified by comparing expression profiles in human colon biopsies of tumour tissue and normal tissue. A separation of the cell lines based on the tumour stage of the original adenocarcinoma was observed after PCA of expression data of the subset of colon cancer-specific genes in the cell lines. The results of this study may be useful in the ongoing research into mechanisms of cancer prevention by dietary components.

Evaluation of the Mytilus galloprovincialis Lam. digestive gland metallothionein as a biomarker in a long-term field study: seasonal and spatial variability.

A study was made of seasonal and spatial variability of metallothionein (MT) concentrations, determined spectrophotometrically in the soluble fraction of the digestive gland of mussels Mytilus galloprovincialis, collected between 1999 and 2001 from several coastal and estuarine locations along the central Eastern Adriatic coast (Croatia). The seasonal influence on the MT and metal concentrations (higher values in winter-spring season, than in summer-autumn season) is more pronounced than the local site-specific influence. Furthermore, within each season a significant site-specific dependence on the MT and trace metal variations can be detected. An inverse relationship of mussel condition index (CI) and temperature with MT and trace metals levels indicates the influence of food abundance and mussel annual reproductive cycle. Substantially higher concentrations of both MT and Cd were recorded in mussels inhabiting estuarine locations, possibly indicating a markedly higher Cd bioavailability at these locations. The positive correlations obtained between MT and Cd in all seasons except autumn support an argument for application of digestive gland MT as a biomarker of Cd exposure, providing evidence for assessing the most appropriate season for mussel sampling.

Do aberrant crypt foci have predictive value for the occurrence of colorectal tumours? Potential of gene expression profiling in tumours.

The effects of different dietary compounds on the formation of aberrant crypt foci (ACF) and colorectal tumours and on the expression of a selection of genes were studied in rats. Azoxymethane-treated male F344 rats were fed either a control diet or a diet containing 10% wheat bran (WB), 0.2% curcumin (CUR), 4% rutin (RUT) or 0.04% benzyl isothiocyanate (BIT) for 8 months. ACF were counted after 7, 15 and 26 weeks. Tumours were scored after 26 weeks and 8 months. We found that the WB and CUR diets inhibited the development of colorectal tumours. In contrast, the RUT and BIT diets rather enhanced (although not statistically significantly) colorectal carcinogenesis. In addition, the various compounds caused different effects on the development of ACF. In most cases the number or size of ACF was not predictive for the ultimate tumour yield. The expression of some tumour-related genes was significantly different in tumours from the control group as compared to tumours from the treated groups. It was concluded that WB and CUR, as opposed to RUT and BIT, protects against colorectal cancer and that ACF are unsuitable as biomarker for colorectal cancer. Effects of the different dietary compounds on metalloproteinase 1 (TIMP-1) expression correlated well with the effects of the dietary compounds on the ultimate tumour yield.

Comparison of off-pump and conventional coronary endarterectomy.

OBJECTIVE: This study was designed to compare the early and midterm results of off-pump coronary endarterectomy (OPCE) with those of conventional coronary endarterectomy (CCE) performed with cardiopulmonary bypass. METHODS: From April 1, 1999, until March 1, 2001, 332 patients underwent off-pump coronary artery bypass grafting at our institution. From this total, 44 (13%) of the patients underwent supplementary OPCE (group 1). The results were compared with those for a group of age-, sex-, and risk factor-matched patients undergoing CCE (group 2) at the same institution. The mean follow-up period was 16 months. The indications for operation in group 1 were angina in 16 (36%) of the cases, cardiac failure in 20 (45%), and prognosis in 8 (19%). In group 2 angina was the indication for operation in 11 (25%) of the cases, cardiac failure in 5 (11%), and prognosis in 30 (64%) of the cases. RESULTS: In group 1, 35 patients underwent single and 9 underwent double endarterectomy. The procedures included 32 right coronary artery, 12 left anterior descending artery, 2 lateral circumflex artery, and 7 diagonal branch operations. Three (6.8%) of the patients in group 1 and 2 (4.4%) of the patients in group 2 developed postoperative myocardial infarction (P <.05). One (2.2%) of the patients in group 1 and 2 (4.4%) of the patients in group 2 died in the postoperative period (P <.05). The numbers of patients with perioperative neurologic deficit in groups 1 and 2 were 0 and 7, respectively (P <.001). Although the rate of perioperative myocardial infarction was higher in group 1, mortality, occurrence of other morbid events, intubation time, intensive care stay, and hospital length of stay were less in group 1 than group 2. CONCLUSION: OPCE can be performed safely with morbidity and mortality comparable with those of CCE.

High-protein diets in hyperlipidemia: effect of wheat gluten on serum lipids, uric acid, and renal function.

BACKGROUND: The metabolic effects of diets high in vegetable protein have not been assessed despite much recent interest in the effect of soy proteins in reducing serum cholesterol. OBJECTIVE: We assessed the metabolic effects of diets high in vegetable protein (specifically, wheat gluten) on serum lipids, uric acid concentrations, and renal function. DESIGN: Twenty hyperlipidemic men and women consumed isoenergetic test (high-protein) and control metabolic diets for 1 mo in a randomized crossover design. In the high-protein diet, 11% of the total dietary energy from starch in the control bread was replaced by vegetable protein (wheat gluten), resulting in 27% of total energy from protein compared with 16% in the control diet. In other respects, the 2 diets were identical. RESULTS: Compared with the control, the high-protein diet resulted in lower serum concentrations of triacylglycerol (by 19.2 +/- 5.6%; P = 0.003), uric acid (by 12.7 +/- 2.0%; P < 0.001), and creatinine (by 2.5 +/- 1.1%; P = 0.035) and higher serum concentrations of urea (by 42.2 +/- 5.8%; P < 0.001) and a higher 24-h urinary urea output (by 99.2 +/- 17.2%; P < 0.001). No significant differences were detected in total or HDL cholesterol or in the renal clearance of creatinine. LDL oxidation, assessed as the ratio of conjugated dienes to LDL cholesterol in the LDL fraction, was lower with the high-protein diet (by 10.6 +/- 3.6%; P = 0.009). CONCLUSIONS: High intakes of vegetable protein from gluten may have beneficial effects on cardiovascular disease risk by reducing oxidized LDL, serum triacylglycerol, and uric acid. Further studies are required to assess the longer-term effects on renal function.

Effect of coronary sinus diastolic balloon pulsation on ischemic myocardium.

OBJECTIVES: To evaluate the effect of coronary sinus diastolic balloon pulsation (CSDBP) on acute myocardial ischemia and infarction. It was hypothesized that this procedure would improve retrograde flow to ischemic areas and allow for more complete oxygen exchange and venous washout of metabolites, with elevated coronary sinus pressure and retrograde pulsation. ANIMALS AND METHODS: This two-part study was done on 10 dogs. First, CSDBP was applied to normal myocardium by a balloon catheter and a pump system at beat to beat cardiac cycles of 1:1, 2:1 and 3:1. Then coronary ischemia was obtained by coronary artery ligation and the procedure was repeated. Electrocardiographic (ECG), arterial and coronary sinus pressure alterations were monitored continuously, and arterial, mixed venous and coronary sinus blood lactate concentrations were measured at each stage of the study. RESULTS: In the first stage no hemodynamic deterioration was observed. In the second stage, mean ECG-ST segment elevation was 6.30+/-0.95 mm (P<0.01) and coronary sinus blood lactate concentration increased to 5.37+/-0.37 mmol/L from 1.95+/-0.31 mmol/L (P<0.01). ECG-ST segment elevation decreased to 3.73+/-0.64 mm and coronary sinus blood lactate concentration decreased to 4.79+/-0.28 mmol/L (P<0.05) with 1:1 beat to beat CSDBP. ECG-ST segment elevation decreased to 2.95+/-0.73 mm and coronary sinus blood lactate concentration decreased to 4.4+/-0.22 mmol/L with 2:1 CSDBP. ECG-ST segment elevation decreased to 3.6+/-0.42 mm and coronary sinus blood lactate concentration decreased to 4.17+/-0.22 mmol/L with 3:1 CSDBP as well. DISCUSSION: Results showed that CSDBP technique lowered the increased ECG-ST segment elevation and myocardial lactate production.

Analysis of metallothioneins by the modified Brdicka procedure.

Quantitative analysis of metallothioneins (MTs) by the modified Brdicka procedure is based on the evaluation of the catalytic hydrogen signal (Cat). The effect of the basic physico-chemical parameters, the temperature and the depolarizer concentration (Co(NH(3))(6)Cl(3)), on the Cat signal height and the respective calibration straight lines was studied by means of the differential pulse (DP) mode at the hanging mercury drop electrode (HMDE). The temperature was varied from 7 to 18 degrees C, and the depolarizer concentration from 1.2x10(-4) to 1.0x10(-3) M Co(NH(3))(6)Cl(3). The commercially available rabbit liver MT was used as the calibrant. The parameters of the calibration straight lines, the standard errors of the intercept s(a) and the slope s(b) were evaluated by means of the least-square method. The hypothesis of a significant difference of the estimated value of the intercept on y-axis compared to the zero value was statistically tested. For those conditions for which this hypothesis was rejected the measuring conditions of the catalytic hydrogen signal are selected and they refer to a buffer 1M (NH(4)Cl+NH(4)OH), pH 9.5, (7.0+/-0.5) degrees C and the depolarizer concentration (0.8 or 1.0)x10(-3) M Co(NH(3))(6)Cl(3).

Arginine intake and risk of coronary heart disease mortality in elderly men.

From experimental studies, the hypothesis is derived that the amino acid arginine, the precursor of NO, could restore the impaired endothelial function and increased platelet activation observed in atherosclerosis. We investigated whether dietary intake of arginine is associated with reduced coronary heart disease risk in elderly persons. The study population consisted of 806 men aged 64 to 84 years at baseline who participated in the Zutphen Elderly Study, a population-based cohort followed up for 10 years. Information about habitual food consumption was collected by use of the cross-check dietary history method. Ninety (11.2%) of the 806 men died from coronary heart disease. Mean+/-SD baseline arginine intake was 4. 35+/-1.07 g/d. Meat was the main source of arginine intake (37.1%), followed by bread (13.1%) and milk and milk products (12.1%). Arginine intake was not associated with coronary heart disease mortality. After adjustment for age, the relative risk (RR) for the medium tertile of arginine intake was 0.72 (95% CI 0.44 to 1.18), and the RR for the highest tertile was 0.71 (95% CI 0.43 to 1.19, P: for trend=0.19) compared with the lowest tertile of arginine intake. After additional adjustment for history of coronary heart disease and diabetes mellitus, energy intake, body mass index, smoking habit, physical activity, and other relevant dietary and biological risk factors, the RR was 1.86 (95% CI 1.06 to 3.27) for the medium intake and 1.56 (95% CI 0.83 to 2.93) for the highest intake (P: for trend=0.17). These results do not support the hypothesis that dietary arginine intake lowers the risk of coronary heart disease mortality.

Advantages and disadvantages of voltammetric method in studying cadmium-metallothionein interactions.

A sensitive and chemical species-selective technique of differential pulse anodic stripping voltammetry (DPASV) was applied in studying the cadmium-metallothionein (Cd-MT) interaction. The amperometric titrations of the purified MT20 and MT10 fractions, isolated by verified biochemical procedures from the digestive gland of cadmium-exposed mussels Mytilus galloprovincialis, with Cd2+ ions were performed in the buffered sodium chloride solution of 0.59 M ionic strength, pH 7.9 and 25 degrees C. Applying the DPASV method at various cadmium to metallothionein ratio several groups of chemical species were recorded. The data on the available ligand concentration to complex cadmium ions (CL), the apparent concentration stability constants (K,) of the respective complexes and the reliability of the determined complexing parameters are discussed. In quantifying the Cd-MT interaction the interference of dithiotreitol (DTT), which is used as the reducing agent in isolation and purification of MTs, is documented.

Determination of the etiological organism during acute exacerbations of COPD and efficacy of azithromycin, ampicillin-sulbactam, ciprofloxacin and cefaclor. Turkish Thoracic Society COPD Working Group.

Acute exacerbations, most of which are due to lower respiratory tract infections, cause great morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD) and most of these are due to lower respiratory tract infections. The aim of this study was to determine the causative organism and the effects of azithromycin, ampicillin sulbactam (sultamicillin), ciprofloxacin and cefaclor monohydrate therapy in COPD. One hundred and six patients with COPD in acute exacerbation were randomized into four groups for empiric antibiotic treatment following lung function tests and sputum examination. The most common strains isolated from sputum were Haemophilus influenzae (30.8%), Streptoccocus pneumoniae (12%) and Moraxella catarrhalis (7.7%). Azithromycin, sultamicillin, ciprofloxacin and cefaclor monohydrate were found to be effective in treating COPD exacerbations.

Easy closure of sternotomy by the Erk needleholder.

Conventional needleholders have elastic arms and lock with the aid of three or four triangle-shaped teeth ends on the arms. Because of these springs, the needle is not absolutely fixed. The Erk needleholder has thick, rigid and strong arms. Locking is obtained by the counter-balancing system and it securely holds the needle.

Thyroid hormone alterations during and after cardiopulmonary bypass.

The haemodynamic effects of thyroid hormones are well known and include those on heart rate, contractility and myocardial oxygen consumption. Cardiopulmonary bypass produces various alterations in endocrine homoeostasis and may exert important haemodynamic effects postoperatively. The purpose of this prospective study was to determine the relation of cardiopulmonary bypass to changes in thyroid function. Blood samples were obtained from 20 patients preoperatively, at specific times before, during and after cardiopulmonary bypass. Total thyroxin (TT4), total triiodothyronine (TT3), free thyroxin (fT4), free triiodothyronine (fT3), thyroid-stimulating hormone (TSH), thyroid-binding globulin (TBG) and albumin were measured by radioimmunoassay and competitive immunoassay. Values of TT4, TT3 and fT3 were significantly depressed up to 24 h after cardiopulmonary bypass (P < 0.05). TSH and fT4 levels remained within normal ranges at all sampling times. It is increasingly evident that cardiopulmonary bypass affects thyroid hormone metabolism, leading to a transient depression characterized by low levels of circulating TT4, TT3 and fT3.

Gigantic patent ductus arteriosus--report of a newborn cadaver dissection and review of the literature.

During the gross anatomical dissection of the thoracic region in a newborn, a gigantic patent ductus arteriosus was found. This vessel had a diameter as large as the pulmonary trunk and a longer length. The brachiocephalic a. and the left common carotid a. originated from the aortic arch in close proximity with each other. The descending aorta showed a dilatation at the junction of this large-bored patent ductus arteriosus. We were unable to find any similar case in the published literature. Knowing that the anatomical variations of the great vessels may cause confusion during surgery or evaluation of CT and MRI scans, this rare case with a huge patent ductus arteriosus is presented.

Tracheoinnominate artery fistula following tracheostomy.

Tracheoinnominate artery fistula is a relatively rare but highly lethal complication occurring in patients with long-standing tracheostomies. Early evaluation of this problem and prompt aggressive therapy are necessary. When massive haemorrhage begins, immediate arterial compression, control of the airway and subsequent treatment of the injured artery may be lifesaving. Immediate surgical exploration through a median sternotomy is necessary to control the proximal and distal innominate artery. After the damaged artery has been excised, vascular reconstruction can be performed to preserve the connection between the proximal and distal ends of the innominate artery. A pedicled pericardial patch was successfully used for the tracheal reconstruction.

Pericardial and pulmonary involvement in rheumatoid arthritis in Turkey.

Pericardial and lung involvement in rheumatoid arthritis (RA), suspected to be less severe in a developing nation (Turkey), have been evaluated. We have studied clinical, echocardiographic and pulmonary findings (radiological and functional) in 93 consecutive Turkish patients with definite/classical RA. Findings were compared with those of a group of patients with osteoarthritis or local rheumatological conditions (n = 60) in a blind protocol. Fifty patients with systemic lupus (SLE) were studied as a high risk control group for pericardial involvement. While pericardial disease was detected in 5.5% (5/90) of RA patients, it was detected in 6.6% (4/60) of the control patients. SLE patients had a 26% (13/50) prevalence. Interstitial lung disease was found in 27.7% of RA patients but it was present in 6.6% (4/60) of the control patients. We observed that a group of patients with RA in Turkey had a low prevalence of pericardial disease. This is further evidence that RA has a mild course in developing countries.