The Brief Repeatable Battery: psychometrics and normative values with age, education and gender corrections in a Serbian population.

Cognitive impairment is present in up to 65 % of multiple sclerosis (MS) patients. The Brief Repeatable Battery of neuropsychological tests (BRB) is one of the most used neuropsychological tools for cognitive assessment in MS. However, relative lack of normative data limits its application in research and clinical practice. In order to obtain normative data for a Serbian population, we administered the BRB version A to 140 healthy subjects and assessed the influence of demographic factors such as gender, age, and education on the tests' scores. We also calculated corrections for these factors. Higher education was associated with better performance on all the tests. Age influenced all the tests, except the word list generation, higher age being associated with worse performance on all other tests. Women performed worse on the paced auditory serial addition test 2, no other gender differences were observed. Our data obtained for the Serbian population could further improve use of the BRB in clinical practice and for the research purposes, establishing cognitive evaluation as a part of standard neurological examination of MS patients.

Transposition of greater omentum in deep sternal wound infection caused by methicillin-resistant Staphylococci, with differing clinical course for MRSA and MRSE.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE) are an increasing problem in deep sternal wound infections (DSWI) after cardiac surgery. METHODS: Between 2005 and 2009, recalcitrant methicillin-resistant Staphylococcus was found in 21 patients with complicated DSWI, and a transposition of the greater omentum (TGO) was finally performed. A positive microbial culture at the time of procedure was present in all patients. The hospital course was reviewed discretely for MRSA and MRSE. RESULTS: Median patient age was 72.3 years (range 60.8-79.7); 76 % of patients were male. Time from the first sternal revision until consecutive open wound therapy due to re-infection and total hospital stay was longer for MRSA compared to MRSE (38 vs. 14 days, P = 0.003, and 141 vs. 91 days, P = 0.007, respectively). The period from cardiac surgery to TGO was likewise prolonged for MRSA (78 vs. 55 days, P = 0.045), whereas in-hospital mortality and one-year mortality rate did not differ. CONCLUSION: TGO remains a good treatment option for DSWI type IV. Microbial findings determine the clinical course; nevertheless in-hospital mortality remains low for both MRSA and MRSE infection.

A procedure for identifying significant environmental aspects in sea ports.

A new methodology has been designed to identify and rank the significant environmental aspects in sea ports. The main objective of the Strategic Overview of Significant Environmental Aspects (SOSEA) is to help port managers to identify significant environmental aspects and to reinforce the awareness about them in order to prioritise work in environmental management. Developed in close collaboration with port environmental managers and tested in a set of ports, it is a user-friendly tool that can be applied in approximately half a working day. It is based on ISO 14001 vocabulary and requirements and it can be considered as the base for the implementation of any Environmental Management System for port communities.

Thalidomide impairment of trinitrobenzene sulphonic acid-induced colitis in the rat - role of endothelial cell-leukocyte interaction.

1. Immune response-modulating drugs such as thalidomide may be of therapeutic value in the treatment of chronic inflammatory bowel diseases including Crohn's disease (CD). In the present study, we have investigated whether thalidomide exerts this effect by impairing endothelial cell-leukocyte interaction through down-regulation of the expression of pro-inflammatory gene products in these cells. 2. Transient CD-like colitis was induced in male Wistar rats by single enema with trinitrobenzene sulphonic acid (TNBS) in ethanol followed by macroscopic scoring, histology, intravital microscopy, RT - PCR and immunohistochemistry (IHC) analyses. Thalidomide or its analogue supidimide were administered in olive oil by intragastric instillation 6 h prior to the induction of colitis and then daily for one week. 3. Both thalidomide and supidimide (200 mg kg(-1) d(-1)) significantly attenuated TNBS-induced colitis as compared to vehicle-treated control animals (44 and 37% inhibition, respectively), and this effect persisted for 7 days post cessation of thalidomide treatment (46% inhibition). 4. Moreover, thalidomide significantly reduced leukocyte sticking to postcapillary venular endothelial cells in the submucosa (by 45%), improved functional capillary density and perfusion, and attenuated endothelial interleukin-8 expression, as judged by IHC analysis. According to RT - PCR analysis, both thalidomide and supidimide also significantly reduced vascular cell adhesion molecule-1 mRNA expression in the affected part of the descending colon. 5. These findings suggest that thalidomide and one of its derivatives impairs CD-like TNBS-induced colitis in the rat by down-regulating endothelial adhesion molecule and chemokine expression and, as a consequence, the interaction of these cells with circulating leukocytes.

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.

A peritoneal cavity chamber for intravital microscopy of the liver under conditions of pneumoperitoneum.

BACKGROUND: Intravital microscopy allows direct visualization of the hepatic microvasculature. We report on a novel application of this technique using a chamber model that simulates the conditions of pneumoperitoneum. METHODS: For this purpose, we designed a peritoneal cavity chamber for rats. In the present study, we evaluated the technical procedure without any induction of increased intraabdominal pressure to assess undisturbed hepatic microcirculation. Intravital microscopy of the liver was performed in 12 rats. Animals that underwent the same operative procedure without the chamber served as controls (n = 12). RESULTS: Hepatic sinusoidal perfusion rate, leukocyte-endothelial cell interaction, and bile flow showed no significant differences between the groups. Operating time was longer in the chamber group. CONCLUSION: The peritoneal cavity chamber is an attractive approach for the study of hepatic microvascular, cellular, and molecular mechanisms that are important to our understanding of the potential harmful effects of laparoscopy on hepatic circulation and liver function.

The Self Diagnosis Method. A new methodology to assess environmental management in sea ports.

A methodology has been designed to assess the performance of the environmental management in sea ports. The Self Diagnosis Method, developed by two research teams and about sixty sea ports, allows the comparison of the current environmental situation with that corresponding to previous years and the assessment of the opportunities for improvement. The main objective is to review the management activities and procedures that affect the environment and the way the port authority handles significant environmental aspects. It has been designed as a "first level" tool: it can be applied in approximately six hours by a non-expert user. It is based on the ISO 14001 vocabulary, requirements and structure, and it can be considered as a first step in the voluntary implementation of an environmental management system for port communities.

Novel chimney-graft technique for preserving hypogastric flow in complex aortoiliac aneurysms.

We describe the feasibility and result of a novel approach to preserve pelvic perfusion during endovascular aortoiliac aneurysm repair (EVAR) in patients with aortoiliac aneurysms extending to the iliac bifurcation. The iliac chimney-graft technique consists of the deployment of a ViaBahn™ graft into the hypogastric artery in combination with standard abdominal aortic stent-grafts. The chimney graft was deployed using a transsubclavian access and placed parallel with the iliac limb into the standard aortic stent graft, which was deployed directly before. The technical procedure was successful. Postoperative control showed a sufficiently excluded aneurysm without evidence of endoleak and good distal perfusion of both iliac arteries. The CT-scan after 6 months confirmed the result. The chimney-graft stent grafts to maintain perfusion to hypogastric arteries are feasible and provide an alternative to hypogastric artery exclusion or branched grafts. Long-term follow-up is needed to evaluate stent-graft patency and failure rates.

Novel chimney-graft technique for preserving hypogastric flow in complex aortoiliac aneurysms.

We describe the feasibility and result of a novel approach to preserve pelvic perfusion during endovascular aortoiliac aneurysm repair (EVAR) in patients with aortoiliac aneurysms extending to the iliac bifurcation. The iliac chimney-graft technique consists of the deployment of a ViaBahn™ graft into the hypogastric artery in combination with standard abdominal aortic stent-grafts. The chimney graft was deployed using a transsubclavian access and placed parallel with the iliac limb into the standard aortic stent graft, which was deployed directly before. The technical procedure was successful. Postoperative control showed a sufficiently excluded aneurysm without evidence of endoleak and good distal perfusion of both iliac arteries. The CT-scan after 6 months confirmed the result. The chimney-graft stent grafts to maintain perfusion to hypogastric arteries are feasible and provide an alternative to hypogastric artery exclusion or branched grafts. Long-term follow-up is needed to evaluate stent-graft patency and failure rates.

Policy development and the estuary environment: a Severn Estuary case study.

The paper reviews the development of key policy relating to estuary management, highlighting the trends and drivers in policy development which have shaped the management and protection of the estuary environment. Focusing on policy developments over the last three decades, the paper draws attention to the significant influence of European policy and new approaches to environmental governance in stimulating wider and more integrated approaches to the environmental management of the estuary, as well as highlighting considerable environmental improvements associated with increased environmental regulation. The paper discusses how 'fit for purpose' the policy framework is to address current challenges, including those identified by recent stakeholder consultations. Significant issues include limited understanding and information related to the cause-effect relationships between policy and environmental quality as well as ongoing institutional and policy fragmentation associated with devolutionary processes. Such fragmentation, alongside under-investment in integrated estuary planning, is likely to prove a particular challenge to balanced and informed decision-making. Whilst the paper focuses on the Severn experience, the approach adopted will be of interest to all assessing policy-environment linkages.

[Another case of "Lazarus phenomenon" during surgery? Spontaneous return of circulation in a patient with a pacemaker]. / Intraoperatives "Lazarus-Phänomen"? Spontane Kreislaufstabilisierung bei einem Patienten mit Herzschrittmacher.

A case is presented of spontaneous return of circulation after cardiac arrest in a patient with a pacemaker without intraoperative resuscitation. In the literature this kind of situation is called the Lazarus phenomenon. Cardiac arrest of the patient occurred during surgery and because of the poor prognosis no cardiopulmonary resuscitation was initiated. After 6 min of apnoea and cessation of circulation, the circulation restarted spontaneously and surgery was continued. Afterwards the patient was transferred to the intensive care unit but died 2 days later without regaining consciousness. The pathophysiological mechanisms for the Lazarus phenomenon are poorly understood but several mechanisms and multifactorial events are discussed in the literature.

STAT-1 decoy oligonucleotide improves microcirculation and reduces acute rejection in allogeneic rat small bowel transplants.

During acute rejection leukocyte-endothelial cell interaction fuelled by costimulatory molecules such as the CD40/CD154 receptor/ligand dyad disrupts microcirculation of the small bowel. Downregulating endothelial CD40 expression by employing a decoy oligonucleotide (dODN) neutralizing the transcription factor signal transducer and activator of transcription-1 (STAT-1) may protect the graft. Therefore allogenic small bowel transplantation was performed in the Brown Norway to Lewis rat model. Graft vessels were pretreated with STAT-1 dODN, mutant control ODN (20 microM) or vehicle (n=8). CD40 antisense ODN and scrambled control ODN-treated transplants served as target control (n=3 each). Intravital microscopy, histology, immunohistochemistry and Western blot analyses were performed 7 days later. Functional capillary density, red blood cell velocity and perfusion index in STAT-1 dODN and CD40 antisense ODN-treated transplants were improved whereas stasis index was reduced. Leukocyte-endothelial cell interaction showed no difference. Histological parameters of rejection, infiltrating CD3-positive cells and apoptotic bodies were also reduced in STAT-1 dODN and CD40 antisense ODN-treated transplants 7 days post-transplantation. CD40 protein abundance was reduced to less than 10% of control in STAT-1 dODN-treated grafts. STAT-1 dODN blockade of CD40 expression improves mucosal perfusion, reduces graft rejection, T-cell infiltration and apoptosis in rat small bowel allografts during acute rejection.

CD40 antisense oligonucleotide inhibition of trinitrobenzene sulphonic acid induced rat colitis.

BACKGROUND: CD154/CD40 interactions play a pivotal role both in humoral and cellular immune responses. Their involvement in the pathogenesis of chronic inflammatory bowel disease (IBD) has been revealed by increased expression of CD40 and CD154 in the inflamed mucosa of patients and the therapeutic effects of anti-CD154 antibodies in experimental colitis. Because of adverse side effects however, the use of such antibodies in patients with IBD may be limited. AIMS: An alternative approach to blocking CD154/CD40 interactions by employing a CD40 antisense oligonucleotide (ODN) was explored. RESULTS: After sequencing of the rat CD40 gene, five antisense ODNs were designed, of which one (rAS3) effectively downregulated CD40 expression in rat vascular smooth muscle cells as well as the subsequent changes in gene expression in response to CD40 stimulation. The therapeutic potency of rAS3 was evaluated in the 2,4,6-trinitrobenzene sulphonic acid (TNBS) induced colitis model of the rat. Single intracolonic injection of a liposomal formulation of rAS3 either prior to or post colitis induction markedly suppressed the inflammatory reaction in these animals monitored both macroscopically and microscopically over one week, while application of a scrambled control ODN had no such effects. Moreover, reverse transcription-polymerase chain reaction analyses revealed reduced expression of vascular cell adhesion molecule 1, interleukin 12 p40, and monocyte chemoatractive protein 1 in the inflamed mucosa, which in turn may have contributed to the decrease in leucocyte infiltration judged by immunohistochemistry. CONCLUSIONS: These results suggest that CD40 antisense ODNs effectively interfere with CD154/CD40 interactions in vivo and, therefore, may provide a novel approach to the treatment of patients with chronic IBD.

Impact of vasoactive intestinal polypeptide and gastrin-releasing peptide on small bowel microcirculation and mucosal injury after hepatic ischemia/reperfusion in rats.

BACKGROUND AND AIMS: Alterations in microvascular perfusion of the intestine after hepatic ischemia/reperfusion have been suggested as an important cause of postoperative septic complications. We therefore investigated small bowel microcirculation and mucosal injury after liver ischemia/reperfusion in a rat model. Furthermore, we analyzed the effects of the regulatory peptides vasoactive intestinal polypeptide and gastrin-releasing peptide for their splanchnic vasoactivity. METHODS: Hepatic ischemia was induced by clamping of the left hepatic artery and vein for 40 min, followed by 60 min of reperfusion. The control group was treated similarly, but without clamping of the liver vessels. Ten minutes after clamping of the hepatic vessels, vasoactive intestinal polypeptide or gastrin-releasing peptide, respectively, were continuously infused intravenously in the experimental groups. Small bowel microcirculation and mucosal injury were assessed using intravital microscopy and the Chiu-score, respectively. RESULTS: The functional capillary density of the small intestine following ischemia and reperfusion of the left hepatic lobe significantly decreased compared to normal controls in both the mucosa and the smooth intestinal muscle. Red blood cell velocity decreased, whereas leukocyte-endothelium adherence, stasis index and the mucosal injury score increased. Administration of vasoactive intestinal polypeptide resulted in an increase of functional capillary density in the mucosa and of the red blood cell velocity and a decrease in the stasis index. The mucosal injury score was significantly higher in reperfused animals without treatment. The application of gastrin-releasing peptide resulted in an isolated increase of the red blood cell velocity. Leukocyte adherences could not be altered by the regulatory peptides. CONCLUSION: We conclude that hepatic ischemia/reperfusion injury leads to significant alterations of small bowel microcirculation and mucosal injury. Vasoactive intestinal polypeptide and gastrin-releasing peptide attenuate the damage in a different manner.

[Clinical importance of measurement of ionized calcium in the blood]. / Klinicki znacaj merenja ionizovanog kalcijuma u krvi.

The paper presents new views concerning clinical significance of determining ionized calcium (Ca2+) in the blood for diagnosis, monitoring and therapy of different illnesses. The clinical usefulness, specificity and sensitivity of determining ionized Ca2+ as the only one physiologically active form has been discussed versus determining the total amount of blood calcium the greatest part of which is in bound (inactive) form.

[Clinical significance of 5'-nucleotidase]. / Klinicki znacaj enzima pet-nukleotidaza.

The paper deals with the current data of molecular organization, localization, activity and clinical significance of 5'-nucleotidase in the diagnosis of different illnesses. The paper also deals with the specificity and sensitivity of 5'-nucleotidase comparing to other laboratory tests.

Alterations in synaptosomal membrane Na,K-ATPase of the gerbil cortex and hippocampus following reversible brain ischemia.

The present experiments were designed to determine the kinetic pattern of Na,K-ATPase in the presence of varying concentrations of Na+ and K+ ions in controls and gerbils exposed to 1 and 5 min of ischemia, respectively, and 60 min and 4 days of recirculation following 5 min of transient ischemia. The pattern of Na,K-ATPase activity in the control cerebral cortex and hippocampus is different. The cortical Na,K-ATPase apparently is more resistant in keeping an optimal activity than the enzyme in the hippocampus. After ischemic insult of either 1 or 5 min in duration, the enzyme activity is inhibited in both brain structures. 4 days after 5 min of ischemia, indicating greater flexibility of the cortical enzyme or less damage than in the hippocampus. Furthermore, the data obtained show that only through the enzyme behavior and kinetic parameters is it possible to reach conclusions about the enzyme function or dysfunction under pathological conditions.