No psychological distress in sportsmen aged 45 years and older after cardiovascular screening, including cardiac CT: The Measuring Athlete's Risk of Cardiovascular events (MARC) study.

BACKGROUND: Psychological distress caused by cardiovascular pre-participation screening (PPS) may be a reason not to implement a PPS program. We assessed the psychological impact of PPS, including cardiac computed tomography (CT), in 318 asymptomatic sportsmen aged ≥45 years. METHODS: Coronary artery disease (CAD) was defined as a coronary artery calcium score ≥100 Agatson units and/or ≥50% luminal stenosis on contrast-enhanced cardiac CT. Psychological impact was measured with the Impact of Event Scale (IES) (seven items) on a six-point scale (grade 0-5). A sum score ≥19 indicates clinically relevant psychological distress. A Likert scale was used to assess overall experiences and impact on sports and lifestyle. RESULTS: A total of 275 participants (86.5% response rate, 95% CI 83-90%) with a mean age of 54.5 ± 6.4 years completed the questionnaires, 48 (17.5%, 95% CI 13-22%) of whom had CAD. The median IES score was 1 (IQR 0-2, [0-23]). IES was slightly higher in those with CAD (mean rank 175 vs. 130, p < 0.001). One participant (with CAD) experienced clinically relevant psychological distress (IES = 23). Participants reported numerous benefits, including feeling safer exercising (58.6%, 95% CI 53-65%) and positive lifestyle changes, especially in those with CAD (17.2 vs. 52.1%, p < 0.001). The majority were satisfied with their participation (93.8%, 95% CI 91-97%). CONCLUSION: Cardiovascular PPS, including cardiac CT, causes no relevant psychological distress in older sportsmen. Psychological distress should not be a reason to forego screening in sportsmen.

Bloodstream infections during the onset of necrotizing enterocolitis and their relation with the pro-inflammatory response, gut wall integrity and severity of disease in NEC.

INTRODUCTION: Bacterial involvement is believed to play a pivotal role in the development and disease outcome of NEC. However, whether a bloodstream infection (BSI) predisposes to NEC (e.g. by activating the pro-inflammatory response) or result from the loss of gut wall integrity during NEC development is a longstanding question. OBJECTIVE: We hypothesize that the occurrence of a BSI plays a complementary role in the pathogenesis of NEC. The first aim of the study was to correlate the occurrence of a BSI during the early phase of NEC with intestinal fatty acid-binding protein (I-FABP) levels, as a marker for loss of gut wall integrity owing to mucosal damage, and Interleukin (IL)-8 levels, as a biomarker for the pro-inflammatory cascade in NEC. The second aim of the study was to investigate the relation between the occurrence of a BSI and disease outcome. MATERIAL AND METHODS: We combined data from prospective trials from two large academic pediatric surgical centers. Thirty-eight neonates with NEC, 5 neonates with bacterial sepsis, and 14 controls were included. RESULTS: BSIs occurred in 10/38 (26%) neonates at NEC onset. No association between the occurrence of BSIs and I-FABP levels in plasma (cohort 1: median 11ng/mL (range 0.8-298), cohort 2: median 6.8ng/mL (range 1.3-15)) was found in NEC patients (cohort 1: p=0.41; cohort 2: p=0.90). In addition, the occurrence of BSIs did not correlate with IL-8 (median 1562pg/mL (range 150-7,500); p=0.99). While the occurrence of a BSI was not correlated with Bell's stage (p=0.85), mortality was higher in patients with a BSI (p=0.005). CONCLUSION: The low incidence of BSIs and the absent association of both the markers for loss of gut wall integrity and the pro-inflammatory response during the early phase of NEC, support the hypothesis that the presence of a BSI does not precede NEC.

Intestinal fatty acid-binding protein levels in Necrotizing Enterocolitis correlate with extent of necrotic bowel: results from a multicenter study.

BACKGROUND: Intestinal fatty acid-binding protein (I-FABP) is considered as a specific marker for enterocyte damage in necrotizing enterocolitis (NEC). OBJECTIVE: The purpose of this study was to evaluate the association of plasma and urinary I-FABP levels with the extent of macroscopic intestinal necrosis in surgical NEC. METHODS: We combined data from prospective trials from two large academic pediatric surgical centers. Nine and 10 infants with surgical NEC were included, respectively. Plasma and urinary of I-FABP at disease onset were correlated with the length of intestinal resection during laparotomy. RESULTS: Median length of bowel resection was 10cm (range 2.5-50) and 17cm (range 0-51), respectively. Median I-FABP levels were 53ng/mL (range 6.3-370) and 4.2ng/mL (range 1.1-15.4) in plasma in cohort 1 respectively cohort 2 and 611ng/mL (range 3-23,336) in urine. The length of bowel resection significantly correlated with I-FABP levels in plasma (Rho 0.68; p=0.04 and Rho 0.66;p=0.04) and in urine (Rho 0.92; p=0.001). CONCLUSION: This 'proof of concept' study demonstrates that plasma and urine I-FABP levels at disease onset was strongly associated with the length of intestinal resection in surgical NEC. This offers further evidence that I-FABP levels are a promising biomarker for assessing intestinal necrosis in infants with advanced NEC.

A surgical perspective of the outcome of a multidisciplinary intestinal rehabilitation program for children with short bowel syndrome in The Netherlands.

AIM: In 2001, a multidisciplinary intestinal rehabilitation program, prompted by a nationwide collaboration on intestinal failure (Dutch Registry for Intestinal Failure and Intestinal Transplantation), was started for children who have short bowel syndrome (SBS). This study evaluates this program, focusing on children who have SBS after extensive bowel resection. DESIGN: This is a retrospective cohort study. METHOD: Demographic data, general information on disease status, and outcome of intestinal rehabilitation of patients treated between 2001 and 2009 were collected. Outcome measures were intestinal autonomy, intestinal and/or liver transplantation, and survival. RESULTS: Ten boys and 9 girls, median gestational age 36 weeks, were treated. Eight were referred, 3 times as many as in the period 1991-2000. Causes of SBS were intestinal atresia (3), gastroschisis (2), volvulus (9), necrotising enterocolitis (3), and strangulation (2). The median remaining small-intestinal length was 35 cm (range, 10 to 70 cm). In 14 patients the ileocecal valve was still present. In all patients at least 25% of colon was still present. The median follow-up was 25 months (range, 50 days to 9 years). After a median of 138 days (range, 41 days to 11 years) on total parenteral nutrition, 16 patients (84%) reached intestinal autonomy. Central venous catheter-related complications occurred in all; there were liver function disorders in 68%, and a failure to thrive in 26%. One patient underwent intestinal lengthening. No patient needed intestinal transplantation, but one underwent liver transplantation for intestinal failure-associated liver disease. Overall mortality was 11%: those 2 patients died of abdominal sepsis. CONCLUSION: This specialized intestinal rehabilitation program led to intestinal autonomy in 84% of the patients who had SBS. None of the patients underwent an intestinal transplantation.

Neurenteric cyst--a case report of this rare disorder.

Neurenteric cysts are rare congenital lesions that are believed to be the result of the split notochord syndrome. We report the clinical case of a 5-year-old boy presenting with vague gastrointestinal symptoms and fatigue, who had undergone resection of a small intestine duplication cyst as a newborn. Computed tomography revealed a mediastinal neurenteric cyst with partial destruction of several thoracic vertebrae. Resection of the tumor proved effective. Recognition of this disorder is important: because of its benign nature, the prognosis after surgical resection can be good. If the diagnosis is made in an early stage, unnecessary progressive destruction of surrounding structures may be prevented.

Follow-up for osteoporosis in older patients three years after a fracture.

BACKGROUND: Recently a Fracture and Osteoporosis outpatient clinic (FO clinic) was set up at the University Medical Centre groningen (UMCG) with the aim to optimise case-finding of osteoporosis in older patients with a low-energy fracture. To provide a diagnostic setting before the start of our fo clinic, case-finding was carried out in patients who suffered an 'osteoporotic' fracture in the year prior to the foundation of the FO clinic. During a three years follow up project, osteoporotic patients who needed therapy were identified. METHODS: Patients aged 50 years or older who were seen in the UMCG for a low-energy fracture (shoulder, wrist or hip) one year before that period were asked to participate. The study was carried out in two parts - a telephone questionnaire and measurement of the bone mineral density (BMD). The data were compared with the results of the FO clinic. RESULTS: Of the 191 patients, 88 could be contacted and were analysed. of these 88 patients only 12 had undergone additional investigations for the presence of osteoporosis in the year of the fracture, and only six patients were on antiosteoporosis medication; 45 patients had already suffered an earlier fracture and ten had a more recent subsequent fracture. Measurements three years after their fracture revealed that 55% of the 88 patients had osteoporosis (T-score less than -2.5 SD). CONCLUSION: After a fracture, case-finding for osteoporosis is good clinical practice. In our study more than half of the patients were lost for follow-up after three years. But it is still worthwhile to check whether patients with fractures in the past had the necessary diagnostics and proper therapy. Comparing these results with those of the FO clinic, it is evident, however, that case-finding of osteoporosis after a fracture can be organised most effectively at the location where the patient first attends for treatment of the fracture, namely in the emergency department of the hospital.

Blood sampling from the retro-orbital plexus, the saphenous vein and the tail vein in rats: comparative effects on selected behavioural and blood variables.

We compared the behaviours of rats, and measured various blood parameters, after three blood sampling techniques: orbital puncture while they were under diethyl-ether anaesthesia, blood collection by tail vein puncture under O2-N2O-halothane anaesthesia and puncture of the saphenous vein without anaesthesia. Twelve rats were subjected to the three treatments according to a Latin square design. After each treatment, the behaviour of the rats was automatically monitored using the so-called LABORAS method, which discriminates between grooming, locomotion and inactivity in rats. Based on excitation scores and urine production, it was found that induction of diethyl-ether anaesthesia combined with orbital puncture caused more distress than did the other two blood sampling techniques. The three techniques had no differential effects on the behaviours of grooming, locomotion and inactivity. Collecting 0.5 ml of blood by orbital puncture was +/-7 times faster than doing so by saphenous vein puncture and +/- 15 times faster than collecting blood by tail vein puncture while the rats were under O2-N2O-halothane anaesthesia. The levels of some haematological and plasma variables differed significantly between the three blood collection techniques. These observations may help to select the most appropriate technique of blood sampling with respect to anticipated discomfort in the animals.

NFkappaB decoy oligodeoxynucleotides reduce monocyte infiltration in renal allografts.

Monocyte influx secondary to ischemia-reperfusion conditions the renal allograft to rejection by presentation of antigens and production of cytokines. Monocyte influx depends on NFkappaB-dependent transcription of genes encoding adhesion molecules and chemokines. Here we demonstrate that cationic liposomes containing phosphorothioated oligodeoxynucleotides (ODN) with the kappaB binding site serving as competitive binding decoy, can prevent TNF-alpha-induced NFkappaB activity in endothelial cells in vitro. In an allogenic rat kidney transplantation model (BN to LEW), we show that perfusing the renal allograft with this decoy prior to transplantation abolishes nuclear NFkappaB activity in vivo and inhibits VCAM-1 expression in the donor endothelium (P<0.05). At 24 h postreperfusion, periarterial infiltration of monocytes/macrophages was significantly reduced in decoy ODN-treated allografts compared to control allografts (3.7+/-0.7 vs. 9.2+/-1.2 macrophages/vessel; P<0.01). At 72 h, there was a reduction of tubulointerstitial macrophage infiltration in decoy ODN-treated kidneys compared to controls (75.6+/-13.9 vs. 120.0+/-11.2 macrophages/tubulointerstitial area; P<0.05). In conclusion, perfusion of the renal allograft with NFkappaB decoy ODN prior to transplantation decreases the initial inflammatory response in a stringent, nonimmunosuppressed allogenic transplantation model. Therefore, the NFkappaB decoy approach may be useful to explore the role of endothelium and macrophages in graft rejection and may be developed into a graft-specific immunosuppressive strategy allowing reduction of systemic immunosuppression on organ transplantation.

Inhibition of inducible nitric oxide synthase improves graft function and reduces tubulointerstitial injury in renal allograft rejection.

Increased levels of nitric oxide (NO) are found in rejecting renal allografts. Inducible NO synthase (iNOS) in infiltrating monocytes/macrophages could lead to NO bursts. NO may modulate the inflammatory response of early rejection due to its high reactivity with superoxide to yield peroxynitrite. To define the role of iNOS in acute renal allograft, rejection effects of the specific iNOS blockers iminoethyl-lysine and 7-butylhexahydro-1H-azepin-2-imine, monohydrochloride on renal function and morphology were investigated in renal allografts. Lewis rats received Brown Norway grafts with one kidney left in situ. All recipients were treated with low dose cyclosporine-A (2.5 mg/kg BW/day s.c.) to allow moderate rejection. In addition, one group received iminoethyl-lysine (10 mg/kg BW/day gavage) and one group received butylhexahydro-azepin-imine (3.4 mg/kg BW/day i.p.). Sham operated Brown Norway donor rats served as baseline controls. Compared to controls, low dose cyclosporine-A decreased glomerular filtration rate (P<0.05) and numerically increased renal vascular resistance. Adding iminoethyl-lysine to cyclosporine-A improved renal hemodynamics. Adding butylhexahydro-azepin-imine to cyclosporine-A practically restored glomerular filtration rate and renal vascular resistance (P<0.05) to control levels. Grafts treated with cyclosporine-A alone showed vascular, glomerular and tubulointerstitial lesions. Adding iminoethyl-lysine or butylhexahydro-azepin-imine to cyclosporine-A did not significantly reduce vascular and glomerular injury, but diminished tubulointerstitial injury as well as nitrotyrosine staining in tubular epithelium (P<0.05). Thus, adding the iNOS blockers iminoethyl-lysine or butylhexahydro-azepin-imine to cyclosporine-A improved graft function and reduced tubulointerstitial lesions.

Proteinuria precedes cerebral edema in stroke-prone rats: a magnetic resonance imaging study.

BACKGROUND AND PURPOSE: Stroke-prone spontaneously hypertensive rats (SHRSP) subjected to high sodium intake develop severe hypertension, cerebral edema, and proteinuria, culminating in organ damage and early death. MRI, which can be applied serially, provides the unique opportunity to study temporal and quantitative relations between these changes and whether diminution of sodium intake can attenuate established cerebral edema. METHODS: SHRSP were subjected to 1% NaCl in drinking water. Cerebral MRI, proteinuria and systolic blood pressure (SBP) were measured serially. After detection of cerebral edema (T2-weighted MRI), 6 rats were killed for histology, to confirm the diagnosis of cerebral edema. The others were followed up for 7 more days while salt loading was continued (n = 10, group 1) or after sodium intake was normalized (n = 7, group 2). RESULTS: SHRSP invariably developed cerebral edema in 30 days (range, 8 to 54 days). At this point neurological signs were absent in 16 of 23 rats. SBP rose until 1 week before detection of cerebral edema, and then stabilized at approximately 265 mm Hg. Proteinuria invariably preceded cerebral edema, with a concentration exceeding 40 mg/d predicting development of cerebral edema in 9 days (range, 3 to 15 days). There was linear correlation (R=.62, P<.0001) between proteinuria and cerebral edema (pixels with an intensity above a defined threshold). Rats in group 1 showed an increase in cerebral edema (from 5.8+/-1.1% to 12.5+/-2.8%; P<.05), and proteinuria remained high (from 305+/-44 to 338+/-29 mg/d); and 2 died spontaneously. Rats in group 2 showed no significant change in edema (from 4.9+/-0.5% to 6.9+/-1.3%) but a marked fall in proteinuria (from 294+/-24 to 119+/-10 mg/d; P<.05), both significantly different from group 1 (P<.05); all survived. SBP remained unaltered in both groups. CONCLUSIONS: Our data establish MRI as a sensitive method for detection of cerebral edema, often prior to neurological signs, in SHRSP. Proteinuria predicts cerebral edema, and these two variables, both obtained noninvasively, are quantitatively related. Moreover, in SHRSP normalizing sodium intake after salt loading attenuates development of cerebral edema and reduces proteinuria.