Hyperglycaemia increases S100ß after short experimental cardiac arrest.

BACKGROUND: Hyperglycaemia is associated with aggravated ischaemic brain injury. The main objective of this study was to investigate the effects on cerebral perfusion of 5 min of cardiac arrest during hyperglycaemia and normoglycaemia. METHODS: Twenty triple-breed pigs (weight: 22-29 kg) were randomised and clamped at blood glucose levels of 8.5-10 mM [high (H)] or 4-5.5 mM [normal (N)] and thereafter subjected to alternating current-induced 5 min-cardiac arrest followed by 8 min of cardiopulmonary resuscitation and direct current shock to restore spontaneous circulation. RESULTS: Haemodynamics, laser Doppler measurements and regional venous oxygen saturation (HbO2) were monitored, and biochemical markers in blood [S100ß, interleukin (IL)-6 and tumour necrosis factor (TNF)] quantified throughout an observation period of 3 h. The haemodynamics and physiological measurements were similar in the two groups. S100ß increased over the experiment in the H compared with the N group (P < 0.05). IL-6 and TNF levels increased across the experiment, but no differences were seen between the groups. CONCLUSIONS: The enhanced S100ß response is compatible with increased cerebral injury by hyperglycaemic compared with normoglycaemic 5 min of cardiac arrest and resuscitation. The inflammatory cytokines were similar between groups.

Effect of tube current on diagnostic image quality in paediatric cerebral multidetector CT images.

The aim of this study was to investigate the effect of tube current on diagnostic image quality in paediatric cerebral multidetector CT (MDCT) images in order to identify the minimum radiation dose required to reproduce acceptable levels of different diagnostic image qualities. Original digital scanning data (raw data) were selected retrospectively from routine MDCT brain examinations of 25 paediatric patients. All examinations had been performed using axial scanning on an eight-slice MDCT (LightSpeed Ultra, GE Healthcare). Their ages ranged from newborn to 15 years. Quantum noise was added artificially to the raw data representing dose reductions equivalent to steps of 20 mA. Patient identification information was removed. Three experienced radiologists blindly and randomly assessed the resulting images from two different levels of the brain with regard to reproduction of structures and overall image quality. Final data were evaluated using the non-parametric statistical approach of inter-scale concordance. The minimum value of tube current-time product (mAs) required to reproduce an image of sufficient diagnostic quality was established in relation to the age of the patient. The corresponding CT dose index values by volume (CTDI(vol) (mGy)) were also established. In conclusion, acceptable reproduction of low-contrast structures was possible at CTDI(vol) values down to 20 mGy (patients 1-5 years old). For acceptable reproduction of high-contrast structures, CTDI(vol) values down to 10 mGy were considered possible (patients 1-5 years old). The original image quality for patients under 6 months of age (15 mGy) was found to be inadequate for acceptable reproduction of low-contrast structures.

Temporary circulatory support with extra corporeal membrane oxygenation in adults with refractory cardiogenic shock.

OBJECTIVE: Early and long-term survival in patients suffering from cardiogenic shock is poor. Treatment with mechanical assist devices is complicated and expensive but claim to improve survival. We reviewed our experience of venoarterial extracorporeal membrane oxygenation (ECMO) in patients with acute cardiogenic shock. DESIGN: ECMO was used in 52 patients with cardiogenic shock. They were divided into those not operated upon previously (n=19) and those having had cardiac surgery prior to circulatory collapse (n=33). RESULTS: Twenty-six patients were weaned from ECMO. Early mortality for all patients was 48%. Mortality beyond 30 days was 5.8%, with no mortality in the non-cardiotomy group. Long-term survival for patients in the non-cardiotomy group was 63%, as compared to 33% in post-cardiotomy patients (p=0.07). Age over 55 years, female gender or cannulation site did not appear to influence survival. CONCLUSION: Mortality for patients in cardiogenic shock is very high. Treatment with ECMO in patients with refractory cardiogenic shock can be performed with good survival especially in non-surgical patients.

Post-injury treatment with a new antioxidant compound H-290/51 attenuates spinal cord trauma-induced c-fos expression, motor dysfunction, edema formation, and cell injury in the rat.

The neuroprotective efficacy of post-injury treatment with the antioxidant compound H-290/51 (10, 30, and 60 minutes after trauma) on immediate early gene expression (c-fos), blood-spinal cord barrier (BSCB) permeability, edema formation, and motor dysfunction was examined in a rat model of spinal cord injury (SCI). SCI was produced by a longitudinal incision into the right dorsal horn of the T10-11 segment under Equithesin anesthesia. Focal SCI in control rats resulted in profound up-regulation of c-fos expression, BSCB dysfunction, edema formation, and cell damage in the adjacent T9 and T12 segments at 5 hours. Pronounced motor dysfunction was present at this time as assessed using the Tarlov scale and the inclined plane test. Treatment with H-290/51 (50 mg/kg, p.o.) 10 and 30 minutes after SCI (but not after 60 minutes) markedly attenuated c-fos expression and motor dysfunction. In these groups, BSCB permeability, edema formation, and cell injuries were mildly but significantly reduced. These observations suggest that (i) antioxidants are capable of attenuating cellular and molecular events following trauma, and (ii) have the capacity to induce neuroprotection and improve motor function if administered during the early phase of SCI, a novel finding.

Neuroprotective effects of melanocortins in experimental spinal cord injury. An experimental study in the rat using topical application of compounds with varying affinity to melanocortin receptors.

The possibility that local administration of low molecular weight non-peptide compounds with varying affinities at melanocortin receptors in the spinal cord will influence pathophysiological outcome of spinal cord injury (SCI) was examined in a rat model. Five new Melacure compounds ME10092, ME10354, ME10393, ME10431 and ME10501 were used in this investigation. Each compound was dissolved in saline and tested at 3 different doses, i.e. 1 microg, 5 microg and 10 microg total dose in 10 microl applied topically 5 min after SCI. The animals were allowed to survive 5 h and trauma induced edema formation, breakdown of the blood-spinal cord barrier (BSCB) and cell injuries were examined and compared with untreated injured rats. A focal SCI inflicted by an incision into the right dorsal horn of the T10-11 segments resulted in marked edema formation, breakdown of the BSCB to Evans blue albumin and caused profound nerve cell injury in the T9 and the T12 segments. Topical application of ME10501 (a compound with high affinity at melanocortin, MC-4 receptors) in high doses (10 microg) resulted in most marked neuroprotection in the perifocal spinal cord (T9 and T12) segments. On the other hand, only a mild or no effect on spinal cord pathology was observed in the traumatized animals that received ME10092, ME10354, ME10393 and ME10431 at 3 different doses. These observations suggest that non-peptide compounds with varying affinity to melanocortin receptors are able to influence the pathophysiology of SCI. Furthermore, compounds acting at melanocortin, MCR4 receptors are capable to induce neuroprotection in spinal cord following trauma.

A new mechanical connector for distal coronary artery anastomoses in coronary artery bypass grafting: a randomized, controlled study.

OBJECTIVE: A new mechanical anastomotic device was evaluated, aiming at its future use in minimally invasive techniques or limited access surgery in patients undergoing coronary artery bypass grafting. METHODS: Between April and December 2002, a total of 60 patients scheduled for elective multivessel bypass grafting were randomly assigned. One vein graft-coronary artery anastomosis per patient was either performed with the St Jude Medical ATG coronary connector system (n = 30; St Jude Medical Inc, St Paul, Minn) or hand sewn (n = 30). Selective coronary angiography or coronary magnetic resonance imaging of the studied graft and vessel was included in the 6-month follow-up. RESULTS: Twenty-eight of the connectors were successfully implanted. Two patients were excluded from the study because of conversion to hand-sewn anastomoses. Six connector-made anastomoses were bleeding at the anastomotic site. At the time of follow-up (190 postoperative days), all control anastomoses and grafts were patent, whereas 26% of the connector anastomoses were occluded. One graft in each group was patent but with stenosis. CONCLUSION: The St Jude Medical ATG coronary connector system for distal anastomoses represents a new concept for sutureless anastomoses in cardiac surgery. This randomized, controlled study shows lower graft patency for anastomoses performed with the connector than for hand-sewn control anastomoses. It illustrates the importance of controlled studies when evaluating new technical equipment in medicine.

Dysarthria, progressive parkinsonian features and symmetric necrosis of putamen in a family with painful lipomas (Dercum disease variant).

We describe painful subcutaneous lipomatosis in four members of a two-generation family. Lipomas appeared in adulthood, were circumscribed, painful on touch and mainly localized to the trunk and proximal parts of the extremities. The disorder was associated with dysarthria, visual pursuit defect and progressive dystonia. MRI showed bilateral increasing cystic lesions in the basal parts of the putamen. No other abnormalities were detected. The lesions corresponded well with the clinical presentation in the patients. Investigation for mitochondrial disease with muscle biopsy and mitochondrial DNA gave normal results. No consistent biochemical changes were found. The disorder in this family was considered to differ from MERRF with lipomatous lesions and multiple symmetric lipomatosis but compatible with a Dercum disease variant.

Intracellular hepatitis C virus RNA-dependent RNA polymerase activity.

Studies of intracellular hepatitis C virus (HCV) RNA-dependent RNA polymerase activity (RdRp activity) have been limited by the poor replicative capacity of HCV in cell culture. We have developed a method that allows for the measurement of HCV specific RdRp activity in eukaryotic cells. This method is based on the transient expression of the HCV polymerase and its templates under the control of the T7 promoter in the presence of an infection with recombinant vaccinia virus (vTF7-3) expressing the bacteriophage T7 DNA-dependent RNA polymerase. Both negative-strand and positive-strand RNA synthesis were characterised, and the role of the other HCV non-structural proteins for polymerase activity was assessed. With this assay we were able to show that: a) Intracellular HCV RdRp activity is not restricted to, but is higher for templates containing HCV specific sequences, b) The HCV polymerase is active within the polyprotein precursor, c) Cleavage of NS5b from the polyprotein precursor does not determine template specificity, and d) HCV RdRp activity is higher in the presence of the other HCV non-structural proteins and lower within a protease-deficient polyprotein precursor. This method allows the measurement of intracellular HCV polymerase activity and may be used to test substances against the HCV polymerase in search of potential drugs for anti-HCV therapy.

Increased FiO2 improves intrathecal oxygenation during thoracic aortic cross-clamping in pigs.

OBJECTIVES: To investigate the effect of 100% oxygen ventilation on cerebrospinal fluid (CSF) oxygenation in 11 pigs during thoracic aortic cross-clamping. DESIGN: An aorto-aortic shunt was used for control of central hemodynamics and study of hypoperfusion by exsanguination. CSF PO2, PCO2 and pH were continuously monitored before and during clamping. The changes in hemodynamic parameters and intrathecal gas tensions in response to variations in proximal mean aortic pressure and fraction of inspired oxygen (FiO2) were recorded. RESULTS: Baseline CSF PO2 decreased from 4.8 +/- 1.9 to 2.6 +/- 2.2 kPa following aortic occlusion. Increasing FiO2 to 1.0 resulted in a significant increase in CSF PO2 to 4.1 +/- 3.0 with a return to 2.7 +/- 2.1 kPa after reducing FiO2 to 0.4 again. The same variations in FiO2 did not induce any significant changes in CSF PO2 during hypotension. CONCLUSION: Increased FiO2 during experimental thoracic aortic cross-clamping with stable proximal arterial pressure helps to maintain CSF PO2, whereas severe hypotension could not be compensated for by hyperoxemia.

Aspects of the spinal cord circulation as assessed by intrathecal oxygen tension monitoring during various arterial interruptions in the pig.

OBJECTIVE: We sought to study the effect of various modes of interruption of the spinal cord blood supply on intrathecal oxygenation. METHODS: In 24 pigs intrathecal PO (2), PCO (2), and pH were continuously monitored with a multiparameter catheter (Paratrend 7, Biomedical Sensors; Diametrics Medical, Inc, St Paul, Minn) during and after aortic crossclamping or selective interruption of segmental arteries and proximal collateral circulation. RESULTS: Proximal aortic clamping (n = 6) produced complete ischemia, whereas a second clamp close to the celiac trunk (n = 4) partly protected against spinal cord ischemia. This is explained by prevention of the steal phenomenon in the excluded part of the aorta. Adding clamps to the subclavian arteries (n = 6) created complete spinal ischemia as the collateral circulation was interrupted. In another group (n = 4) all segmental arteries below T5 were occluded with no reaction in the intrathecal variables. Additional selective clamping of supreme intercostal arteries (n = 4) showed the relative importance of the subclavian and vertebral collateral pathways. CONCLUSIONS: Continuous intrathecal PO (2) was monitored during various modes of interruption of the spinal cord blood supply. This provided insight into the ischemia mechanisms and relative importance of the segmental contribution and proximal collateral pathways of the spinal cord circulation in pigs. A short literature review is given, and aspects of comparative anatomy are discussed.

HuR, a protein implicated in oncogene and growth factor mRNA decay, binds to the 3' ends of hepatitis C virus RNA of both polarities.

To identify cellular factors that interact with hepatitis C virus RNA, cellular extracts were subjected to UV cross-linking to radiolabeled RNAs corresponding to the hepatitis C virus 5' and 3' untranslated regions of positive and negative polarities. Our results demonstrate that the U-rich region of the hepatitis C virus 3' untranslated region of the positive RNA strand is a hot spot for cellular RNA binding proteins. Two of these proteins were identified as the ELAV-like HuR protein and hnRNP C. Interestingly, HuR and hnRNP C also interacted with the 3' end of the RNA representing the negative strand of the HCV genome. The binding of HuR and hnRNP C to the 3' ends of the HCV RNAs of both negative and positive polarities suggests that HuR and hnRNP C may be involved in the transcription of the HCV RNA genome. Alternatively, they act by protecting the HCV RNAs from premature degradation by binding to their 3' ends. However, we were unable to demonstrate an effect on HCV RNA stability by the HuR protein. These interactions may be necessary for the establishment of chronic active infections that may develop into cirrhosis or hepatocellular carcinoma.

Early outcome and graft patency in mammary artery grafting of left anterior descending artery with sternotomy or anterior minithoracotomy.

BACKGROUND: The main objective of this study was to retrospectively compare early outcome and graft patency in patients who underwent coronary artery bypass grafting with the internal thoracic artery to the left anterior descending artery via an anterior minithoracotomy or median sternotomy and without the use of extracorporeal circulation. METHODS: One hundred thirty consecutive patients were studied. Median sternotomy was performed in 77 patients and anterior minithoracotomy in 53 patients. RESULTS: There were no differences in early clinical data or persistent postoperative pain between the groups. Early graft patency was 88% in the thoracotomy group and 96% in the sternotomy group (p = 0.3). Five of 7 patients who presented with a significant stenosis at the first coronary angiography had a normal angiogram at the reangiography. None of the patients with nonsignificant stenosis at the early coronary angiography had any clinical signs of ischemia or chest pain. CONCLUSIONS: In our experience, anterior minithoracotomy and median sternotomy are different and distinguishable regarding early outcome and early graft patency. Most of the stenoses visualized at the early coronary angiography had vanished at a later coronary angiography, which makes the interpretation of the angiogram hazardous as a tool for the decision for redo procedure in the early postoperative period.

Children with septo-optic dysplasia - how to improve and sharpen the diagnosis.

The data in this article are based on investigations performed in 25 children with suspected septo-optic dysplasia (SOD). There are many signs and methods that help in the diagnosis of SOD. In particular, the ocular fundus, abnormalities of the hypothalamo-pituitary axis and other midline brain structures should be described. In order to achieve a more holistic and functional diagnosis, the degree of neurological, neuropsychiatric and psychological involvement should also be stated. It has been suggested that SOD is associated with autosomal recessive inheritance, and it can be speculated that it is the result of genetic and environmental influences early in gestation. An early diagnosis can favourably influence the outcome of the affected child.

Off-pump bypass surgery--experience of 250 cases.

From April 1996 to October 1998, 250 patients with a mean age of 63 years (31-86 years) underwent coronary artery bypass grafting using the off-pump technique. The prime reason for using this technique was the need to minimize the surgical trauma by avoiding extracorporeal circulation. Fifty-seven percent of the patients had 1-vessel disease, 39% had 2-vessel disease and 4% 3-vessel disease. Sternotomy was performed in 196 patients and an anterior mini-thoracotomy in 54 patients. The mean number of coronary anastomoses was 1.5. Perioperative mortality was 0.4%. The first consecutive 87 patients underwent an early postoperative coronary angiography (days 1-5) revealing a graft patency of 96.5%. Five out of the 7 patients with occluded grafts subsequently underwent another intervention (surgical revascularization in 4 patients and percutaneous transluminal coronary angioplasty in one); 1.2% developed transmural myocardial infarction and 2.8% were reoperated upon for bleeding. The mean time of ventilatory support was 2.5+/-0.5 h. The mean ICU time for all patients was 12 h (0-10 days). The mean in-hospital time was 7 days (2-30 days). Coronary artery bypass surgery without the use of extracorporeal circulation is a safe procedure that can be performed with limited need for intensive care resources. However, long-term results remain to be investigated.

A new method of intrathecal PO2, PCO2, and pH measurements for continuous monitoring of spinal cord ischemia during thoracic aortic clamping in pigs.

BACKGROUND: Impaired spinal cord circulation during thoracic aortic clamping may result in paraplegia. Reliable and fast responding methods for intraoperative monitoring are needed to facilitate the evaluation of protective measures and efficiency of revascularization. METHODS: In 11 pigs, a multiparameter PO2, PCO2, and pH sensor (Paratrend 7, Biomedical Sensors Ltd, United Kingdom) was introduced into the intrathecal space for continuous monitoring of cerebrospinal fluid (CSF) oxygenation during thoracic aortic cross-clamping (AXC) distal to the left subclavian artery. A laser-Doppler probe was inserted into the epidural space for simultaneous measurements of spinal cord flux. Registrations were made before and 30 minutes after clamping and 30 and 60 minutes after declamping. The same measuring points were used for systemic hemodynamic and metabolic data acquisition. RESULTS: The mean CSF PO2 readings of 41 mm Hg (5.5 kPa) at baseline decreased within 3 minutes to 5 mm Hg (0.7 kPa) during AXC (P < .01). Spinal cord flux measurement responded immediately in the same way to AXC. Both methods indicated normalization of circulation during declamping. Significant (P < .01) changes were also observed in the CSF metabolic parameters PCO2 and pH. CONCLUSIONS: In this experimental model of spinal ischemia by AXC, online monitoring of intrathecal PO2, PCO2, and pH showed significant changes and correlated well with epidural laser-Doppler flowmetry (P < .01).

Relationship between intrathecal oxygen tension and ultrastructural changes in the spinal cord during experimental aortic clamping.

OBJECTIVES: To investigate spinal cord ultrastructure related to cerebrospinal fluid (CSF) oxygenation. DESIGN: experimental aortic occlusion model with intrathecal oxygen tension monitoring. MATERIALS AND METHODS: Two groups of pigs underwent proximal (P) or double (D) aortic occlusion for 30 min followed by 1 h of reperfusion. In a third group (I) segmental arteries distal to T3 were clamped for 90 min. A thin pO(2), pCO(2) and pH sensor was placed intrathecally for continuous monitoring of CSF. Spinal cord segments were studied by electron microscopy (EM). RESULTS: In group P, CSF-pO(2)rapidly decreased during clamping and major changes in pH and pCO(2)were seen. EM demonstrated neuronal degeneration with loss of cellular integrity and severe affection of organelles. In the group D, CSF oxygenation decreased to about half, but with only moderate changes in the metabolic parameters. Group I showed no significant changes in CSF measurements. The latter groups were similar at EM, showing only mild mitochondrial changes. CONCLUSIONS: The level of CSF oxygenation during aortic cross-clamping or segmental artery interruption seems to correlate with ultrastructural changes in the spinal cord. This online intrathecal monitoring technique may provide valuable information on spinal cord circulation during thoracoabdominal aortic surgery.

Difficulties in the interpretation of coronary angiogram early after coronary artery bypass surgery on the beating heart.

OBJECTIVE: The major objective of this study was to evaluate the findings in early postoperative coronary angiography in patients who underwent coronary revascularization on the beating heart without cardiopulmonary bypass. METHODS: Eighty-four consecutive patients receiving 113 grafts were studied. A coronary angiography was performed 0 to 5 days postoperatively. All the grafts were reviewed and classified in the following way: grade A (unimpaired run-off); grade B1 (<50 stenosis); grade B2 (>50% stenosis); grade O (occlusion). A second coronary angiography was performed in patients with a stenosis grade B2, 4 to 30 months postoperatively. An exercise test was performed by patients with B1 stenosis. RESULTS: Overall graft patency was 96% in the 113 grafts. None of the 14 patients with B1 stenosis in the early coronary angiography had any clinical signs of ischemia. Eight of the 12 patients who exhibited B2 stenosis either at the anastomotic site, in the graft or in the distal coronary artery at the first coronary angiography had a normal angiogram at the re-angiography. CONCLUSION: A majority of stenoses visualized at the early coronary angiography could not be seen at a later coronary angiography, which makes the interpretation of the angiogram unreliable as a tool for the decision as to redo-procedure in the early postoperative period.

Weaning from mechanical support in a patient with acute heart failure and multiple sclerosis.

We describe a 19-year-old woman developing acute left ventricular heart failure during her first exacerbation of multiple sclerosis. Histopathologic examination of myocardial tissue showed extensive myocytolysis. A left ventricular assist device was implanted. Three months later the cardiac function was restored and the left ventricular assist device was explanted. After 1 year the patient still remains well and her cardiac function is normal.

Influence of segmental spinal cord perfusion on intrathecal oxygen tension during experimental thoracic aortic crossclamping.

PURPOSE: The purpose of this study was to evaluate the possibility of identifying alterations in blood supply to the spinal cord during thoracic aortic crossclamping. METHODS: In 17 pigs, a multiparameter PO(2), PCO(2,) and pH sensor was introduced into the intrathecal space for continuous monitoring of cerebrospinal fluid (CSF) oxygenation during aortic crossclamping. An epidural laser Doppler probe was used to measure spinal cord flux. After insertion of an aortic shunt from the left subclavian to the left iliac artery and interruption of the right subclavian and lumbar arteries (L2-L5), the thoracic aorta just distal to the left subclavian artery was clamped for 60 minutes. By placement of the distal aortic crossclamping below the level of L1 in group A (n = 9 animals), perfusion of only the abdominal visceral arteries was maintained. In group B (n = 8 animals), the distal aortic crossclamping was above the level of T12, and thus some spinal cord perfusion was maintained through the aortic shunt. RESULTS: The significant decrease in CSF PO(2) was observed within 3 minutes after the placement of the proximal aortic crossclamping and was normalized in all animals after establishment of the shunt flow. In group A, distal aortic crossclamping caused a decrease in CSF PO(2) with at least 50% of the preclamping values within 3 minutes. The mean CSF PO(2) of 2.99 +/- 0.70 kPa at 60 minutes of distal aortic crossclamping in group B was significantly higher than in group A (0.11 +/- 0.11 kPa; P <. 001). In group A, PCO(2) measurements showed no significant changes in 3 minutes after distal aortic crossclamping but revealed significantly higher values at 30 and 60 minutes compared with group B. Spinal cord flux values showed similar changes as CSF PO(2) during the whole experiment in both groups. CONCLUSION: In this experimental model of aortic crossclamping, continuous CSF oxygen tension monitoring allows rapid detection of alterations in spinal cord circulation.