Discrepancy in prevalence of Huntington's disease in two Swedish regions.

BACKGROUND: Huntington's disease (HD) is a neurodegenerative disease with an autosomal dominant pattern of inheritance. The prevalence varies between different geographical regions with an estimated average in Europe of about 6/100 000. Parts of northern Sweden are known to have an accumulation of HD, but no prevalence studies have been undertaken for 50 years. OBJECT: The aim of this study was to estimate the prevalence of HD in the two different Swedish counties of Jämtland and Uppsala and compare them with the reported prevalence in Europe. METHOD: Patients registered with the diagnosis of HD were identified through medical records in each county. Presymptomatic patients were excluded. We also compared the annual number of individuals with HD registered in the database of the National Board of Health and Welfare in these regions, with all of Sweden. RESULTS: The prevalence of HD was found to be 22.1/100 000 in Jämtland and 4.9/100 000 in Uppsala county. The mean age was 62.2 years and 61.8 years, respectively. The annual average of patients with HD registered at inpatient care was 1.5/100 000 in Jämtland, 0.44/100 000 in Uppsala county, and 0.56/100 000 in all of Sweden. CONCLUSION: The prevalence of patients with the diagnosis of HD is four times higher in the county of Jämtland than in the county of Uppsala, where the prevalence is more similar to the average in Europe. Our results support earlier findings of regional variations of HD prevalence with an accumulation in certain parts of northern Sweden.

Milrinone and esmolol decrease cardiac damage after resuscitation from prolonged cardiac arrest.

BACKGROUND: Long-term survival after cardiac arrest (CA) due to shock-refractory ventricular fibrillation (VF) is low. Clearly, there is a need for new pharmacological interventions in the setting of cardiopulmonary resuscitation (CPR) to improve outcome. Here, hemodynamic parameters and cardiac damage are compared between the treatment group (milrinone, esmolol and vasopressin) and controls (vasopressin only) during resuscitation from prolonged CA in piglets. METHODS: A total of 26 immature male piglets were subjected to 12-min VF followed by 8-min CPR. The treatment group (n=13) received i.v. (intravenous) boluses vasopressin 0.4 U/kg, esmolol 250 µg/kg and milrinone 25 µg/kg after 13 min, followed by i.v. boluses esmolol 375 µg/kg and milrinone 25 µg/kg after 18 min and continuous esmolol 15 µg/kg/h infusion during 180 min reperfusion, whereas controls (n=13) received equal amounts of vasopressin and saline. A 200 J monophasic counter-shock was delivered to achieve resumption of spontaneous circulation (ROSC) after 8 min CPR. If ROSC was not achieved, another 200 J defibrillation and bolus vasopressin 0.4 U/kg would be administered in both groups. Direct current shocks at 360 J were applied as one shot per minute over maximally 5 min. Hemodynamic variables and troponin I as a marker of cardiac injury were recorded. RESULTS: Troponin I levels after 180 min reperfusion were lower in the treatment group than in controls (P<0.05). The treatment group received less norepinephrine (P<0.01) and had greater diuresis (P<0.01). There was no difference in survival between groups. CONCLUSION: The combination of milrinone, esmolol and vasopressin decreased cardiac injury compared with vasopressin alone.

Adrenaline increases blood-brain-barrier permeability after haemorrhagic cardiac arrest in immature pigs.

BACKGROUND: Adrenaline (ADR) and vasopressin (VAS) are used as vasopressors during cardiopulmonary resuscitation. Data regarding their effects on blood-brain barrier (BBB) integrity and neuronal damage are lacking. We hypothesised that VAS given during cardiopulmonary resuscitation (CPR) after haemorrhagic circulatory arrest will preserve BBB integrity better than ADR. METHODS: Twenty-one anaesthetised sexually immature male piglets (with a weight of 24.3 ± 1.3 kg) were bled 35% via femoral artery to a mean arterial blood pressure of 25 mmHg in the period of 15 min. Afterwards, the piglets were subjected to 8 min of untreated ventricular fibrillation followed by 15 min of open-chest CPR. At 9 min of circulatory arrest, piglets received amiodarone 1.0 mg/kg and hypertonic-hyperoncotic solution 4 ml/kg infusions for 20 min. At the same time, VAS 0.4 U/kg was given intravenously to the VAS group (n = 9) while the ADR group received ADR 20 µg/kg (n = 12). Internal defibrillation was attempted from 11 min of cardiac arrest to achieve restoration of spontaneous circulation. The experiment was terminated 3 h after resuscitation. RESULTS: The intracranial pressure (ICP) in the post-resuscitation phase was significantly greater in ADR group than in VAS group. VAS group piglets exhibited a significantly smaller BBB disruption compared with ADR group. Cerebral pressure reactivity index showed that cerebral blood flow autoregulation was also better preserved in VAS group. CONCLUSIONS: Resuscitation with ADR as compared with VAS after haemorrhagic circulatory arrest increased the ICP and impaired cerebrovascular autoregulation more profoundly, as well as exerted an increased BBB disruption though no significant difference in neuronal injury was observed.

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.

Improved neuroprotective effect of methylene blue with hypothermia after porcine cardiac arrest.

BACKGROUND: Induced mild hypothermia and administration of methylene blue (MB) have proved to have neuroprotective effects in cardiopulmonary resuscitation (CPR); however, induction of hypothermia takes time. We set out to determine if MB administered during CPR could add to the histologic neuroprotective effect of hypothermia. METHODS: A piglet model of extended cardiac arrest (12 min of untreated cardiac arrest and 8 min of CPR) was used to assess possible additional neuroprotective effects of MB when administered during CPR before mild therapeutic hypothermia induced 30 min after restoration of spontaneous circulation (ROSC). Three groups were compared: C group (n = 8) received standard CPR; PH group (n = 8) received standard CPR but 30 min after ROSC these piglets were cooled to 34°C; the PH+MB group (n = 8) received an MB infusion 1 min after commencement of CPR and the same cooling protocol as the PH group. Three hours later, the animals were killed. Immediately after death, the brains were harvested pending histological and immunohistological analysis. RESULTS: Circulatory variables were similar in the groups except that cardiac output was greater in the PH+MB group 2-3 h after ROSC. Cerebral cortical neuronal injury and blood-brain barrier disruption was greatest in the C group and least in the MB group. The neuroprotective effect of MB and hypothermia was significantly greater than that of delayed hypothermia alone. CONCLUSION: Administration of MB during CPR added to the short term neuroprotective effects of induced mild hypothermia induced 30 min after ROSC.

Physical therapy in Huntington's disease--toward objective assessments?

BACKGROUND AND PURPOSE: Physical therapy is recommended for the treatment of Huntington's disease, but reliable studies investigating its efficacy are almost non-existent. This may in part be due to the lack of suitable outcome measures. Therefore, we investigated the applicability of novel quantitative and objective assessments of motor dysfunction in the evaluation of physical therapy interventions aimed at improving gait and posture. METHODS: Twelve patients with Huntington disease received a predefined twice-weekly intervention focusing on posture and gait over 6 weeks. The GAITRite mat and a force plate were used for objective and quantitative assessments. The Unified Huntingtons Disease Rating Scale Total Motor Score, the timed Up &Go test, and the Berg Balance Scale were used as clinical outcome measures. RESULTS: Significant improvements were seen in GAITRite measures after therapy. Improvements were also seen in the Up & Go test and Berg Balance Scale, whereas force plate measures and Total Motor Scores did not change. CONCLUSIONS: The results suggest that physical therapy has a positive effect on gait in Huntington's disease. The study shows that objective and quantitative measures of gait and posture may serve as endpoints in trials assessing the efficacy of physical therapy. They should be explored further in larger trials applying a randomized controlled setting.

Evaluation of image-enhanced paediatric computed tomography brain examinations.

The aim of this study was to evaluate the possibility of reducing the radiation dose to paediatric patients undergoing computed tomography (CT) brain examination by using image-enhancing software. Artificial noise was added to the raw data collected from 20 patients aged between 1 and 10 y to simulate tube current reductions of 20, 40 and 60 mA. All images were created in duplicate; one set of images remained unprocessed whereas the other was processed with image-enhancing software. Three paediatric radiologists assessed the image quality based on their ability to visualise the high- and low-contrast structures and their overall impression of the diagnostic value of the image. For patients aged 6-10 y, it was found that dose reductions from 27 mGy (CTDI(vol)) to 23 mGy (15 %) in the upper brain and from 32 to 28 mGy (13 %) in the lower brain were possible for standard diagnostic CT examinations when using the image-enhancing filter. For patients 1-5 y, the results for standard diagnostics in the upper brain were inconclusive, for the lower brain no dose reductions were found possible.

A method to analyse observer disagreement in visual grading studies: example of assessed image quality in paediatric cerebral multidetector CT images.

The purpose was to demonstrate a non-parametric statistical method that can identify and explain the components of observer disagreement in terms of systematic disagreement as well as additional individual variability, in visual grading studies. As an example, the method was applied to a study where the effect of reduced tube current on diagnostic image quality in paediatric cerebral multidetector CT (MDCT) images was investigated. Quantum noise, representing dose reductions equivalent to steps of 20 mA, was artificially added to the raw data of 25 retrospectively selected paediatric cerebral MDCT examinations. Three radiologists, blindly and randomly, assessed the resulting images from two different levels of the brain with regard to the reproduction of high- and low-contrast structures and overall image quality. Images from three patients were assessed twice for the analysis of intra-observer disagreement. The intra-observer disagreement in test-retest assessments could mainly be explained by a systematic change towards lower image quality the second time the image was reviewed. The inter-observer comparisons showed that the paediatric radiologist was more critical of the overall image quality, while the neuroradiologists were more critical of the reproduction of the basal ganglia. Differences between the radiologists regarding the extent to which they used the whole classification scale were also found. The statistical method used was able to identify and separately measure a presence of bias apart from additional individual variability within and between the radiologists which is, at the time of writing, not attainable by any other statistical approach suitable for paired, ordinal data.

Sex differences in cerebral injury after severe haemorrhage and ventricular fibrillation in pigs.

BACKGROUND: Experimental studies of haemorrhagic shock have documented a superior haemodynamic response and a better outcome in female animals as compared with male controls. Such sexual dimorphism has, nevertheless, not been reported after circulatory arrest that follows exsanguination and shock. We aimed to study differences in cerebral injury markers after exsanguination cardiac arrest in pre-pubertal piglets. The hypothesis was that cerebral injury is less extensive in female animals, and that this difference is independent of sexual hormones or choice of resuscitative fluid. METHODS: Thirty-two sexually immature piglets (14 males and 18 females) were subjected to 5 min of haemorrhagic shock followed by 2 min of ventricular fibrillation and 8 min of cardiopulmonary resuscitation, using three resuscitation fluid regimens (whole blood, hypertonic saline and dextran, or acetated Ringers' solution plus whole blood and methylene blue). Haemodynamic values, cellular markers of brain injury and brain histology were studied. RESULTS: After successful resuscitation, female piglets had significantly greater cerebral cortical blood flow, tended to have lower S-100beta values and a lower cerebral oxygen extraction ratio. Besides, in female animals, systemic and cerebral venous acidosis were mitigated. Female piglets exhibited a significantly smaller increase in neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) expression in their cerebral cortex, smaller blood-brain-barrier (BBB) disruption and significantly smaller neuronal injury. CONCLUSION: After resuscitation from haemorrhagic circulatory arrest, cerebral reperfusion is greater, and BBB permeability and neuronal injury is smaller in female piglets. An increased cerebral cortical iNOS and nNOS expression in males implies a mechanistic relationship with post-resuscitation neuronal injury and warrants further investigation.

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.

Progressive encephalopathy and complex I deficiency associated with mutations in MTND1.

Complex I of the oxidative phosphorylation system is composed of at least 45 subunits, seven of which are encoded by mitochondrial DNA (mtDNA). In this study we have investigated two children with complex I deficiency in muscle mitochondria. Patient 1 had cerebellar ataxia from early infancy and an abnormal MRI of the brain compatible with Leigh syndrome (LS). The course was rapidly progressive with frequent exacerbations and death at 2 years and 10 months of age. Patient 2 had a lactic acidosis in the newborn period and had a severe psychomotor developmental retardation. In her teens she developed hypertrophic cardiomyopathy and died at 26 years of age because of cardiac insufficiency. Sequencing analysis of mitochondrial encoded ND genes (MTND) showed two DE NOVO mutations in MTND1 in both patients. Patient 1 had a novel heteroplasmic G3890A mutation, R195Q. Patient 2 had a heteroplasmic G3481A mutation, E59K. The G3890A mutation in patient 1 is the first identified mutation in MTND1 in association with LS and complex I deficiency. The findings in this patient as well as in patient 2 demonstrate new clinical expressions of mutations in MTND1. The findings in patient 2 also illustrates that MTND mutations may be pathogenic even at a low percentage.

Neuroprotective effects of melanocortins in CNS injury.

New compounds having affinity to various melanocortin receptors have recently been identified as possible neuroprotective agents. This review is focused on the role of neuroprotective effects of melanocortins in CNS injury and repair mechanisms. Using selective non-peptidic compounds with varying affinity to melanocortin receptors, our laboratory has shown their anti-edematous effects in the spinal cord injury. This effect of the compounds is related with their ability to attenuate blood-spinal cord barrier permeability. The functional significance and possible therapeutic strategies of these compounds in CNS injury are discussed.

Dyskinetic cerebral palsy: a population-based study of children born between 1991 and 1998.

The aim of this study was to describe the epidemiology, aetiology, and clinical findings in dyskinetic cerebral palsy (CP)in a population-based follow-up study of children born between 1991 and 1998. Age range at ascertainment was 4 to 8 years and prevalence was 0.27 per 1000 live-births. Forty-eight children were examined (27 males, 21 females; mean age 9y, range 5-13y). Thirty-nine had dystonic CP and nine a choreo-athetotic subtype. Primitive reflexes were present in 43 children and spasticity in 33. Gross Motor Function Classification System levels were: Level IV, n= 10 and Level V, n= 28. The rate of learning disability (n= 35) and epilepsy (n= 30) increased with the severity of the motor disability. Thirty-eight children had anarthria. Peri- or neonatal adverse events had been present in 34 of 42 children born at >or=34 weeks' gestation. Motor impairment was most severe in this group. Placental abruption or uterine rupture had occurred in 8 participants and 19 of the 42 near-term/term children required assisted ventilation, compared with 1% and 12% respectively in other CP types. Neuroimaging in 39 children born at >or=34 weeks revealed isolated, late third trimester lesions in 24 and a combination of early and late third trimester lesions in seven. Dyskinetic CP is the dominant type of CP found in term-born, appropriate-for-gestational-age children with severe impairments who have frequently experienced adverse perinatal events.

Ammonium chloride and alpha-ketoglutaric acid increase glutamine availability in the early phase of induced acute metabolic acidosis.

BACKGROUND: Glutamine deficiency in critical illness is associated with increased morbidity and mortality. We hypothesized that ammonium chloride (NH(4)Cl) and alpha-ketoglutaric acid (alpha-KGA) infusions could increase glutamine availability possibly through de novo synthesis in the liver. METHODS: Anesthetized post-absorptive pigs were allocated to four groups (n = 8). The study groups received either a 4-h intravenous infusion of alpha-KGA, 11.4 micromol/kg/min and NH(4) (+), 9.7 micromol/kg/min (group 1), or alpha-KGA, 2.85 micromol/kg/min and NH(4) (+), 46.3 micromol/kg/min (group 2), or alpha-KGA, 11.4 micromol/kg/min (group 3), or isotonic saline (control group). Plasma concentrations of glutamine and glutamine exchange in liver, intestine and skeletal muscle were investigated. RESULTS: Plasma glutamine concentrations in group 1 (58% increase) were greater (P < 0.05) compared with the control group (14% decrease) and group 3 (13% decrease), and in group 2 (91% increase) compared with the control group, group 3 (P < 0.0001) and group 1 (P < 0.05). Intestinal glutamine extractions in group 2 were significantly greater (P < 0.01) compared with all other groups. Neither the liver nor the hind leg increased its release of glutamine. Arterial pH decreased (all P < 0.001) to 7.39 +/- 0.01 in the control group, 7.30 +/- 0.01 in group 1, 7.19 +/- 0.01 in group 2 and 7.35 +/- 0.01 in group 3. CONCLUSION: Infusions of alpha-KGA and NH(4)Cl, to a pH range of 7.20-7.30, did not enhance hind leg or hepatic glutamine release. The increased plasma concentrations of glutamine were effects of NH(4)Cl, not alpha-KGA, and caused either by de novo synthesis or decreased degradation.

Intracerebral administration of neuronal nitric oxide synthase antiserum attenuates traumatic brain injury-induced blood-brain barrier permeability, brain edema formation, and sensory motor disturbances in the rat.

The role of nitric oxide (NO) in traumatic brain injury (TBI)-induced sensory motor function and brain pathology was examined using intracerebral administration of neuronal nitric oxide synthase (nNOS) antiserum in a rat model. TBI was produced by a making a longitudinal incision into the right parietal cerebral cortex limited to the dorsal surface of the hippocampus. Focal TBI induces profound edematous swelling, extravasation of Evans blue dye, and up-regulation of nNOS in the injured cerebral cortex and the underlying subcortical areas at 5 hours. The traumatized animals exhibited pronounced sensory motor deficit, as seen using Rota-Rod and grid-walking tests. Intracerebral administration of nNOS antiserum (1 : 20) 5 minutes and 1 hour after TBI significantly attenuated brain edema formation, Evans blue leakage, and nNOS expression in the injured cortex and the underlying subcortical regions. The nNOS antiserum-treated rats showed improved sensory motor functions. However, administration of nNOS antiserum 2 hours after TBI did not influence these parameters significantly. These novel observations suggest that NO participates in blood-brain barrier disruption, edema formation, and sensory motor disturbances in the early phase of TBI, and that nNOS antiserum has some potential therapeutic value requiring additional investigation.

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.

Spinal cord injury induced heat shock protein expression is reduced by an antioxidant compound H-290/51. An experimental study using light and electron microscopy in the rat.

The possibility that oxidative stress participates in heat shock protein 72 kD (HSP 72) expression following a focal trauma to the spinal cord was examined using a potent antioxidant compound H-290/51 in a rat model. A focal spinal cord injury (SCI) inflicted by making a longitudinal incision on the right dorsal horn of the T10-T11 segment under equithesin anaesthesia resulted in profound upregulation of HSP 72 expression in the adjacent spinal cord segments T9 and T12. This expression of HSP was most marked in the ipsilateral cord at 5 h after SCI. Pretreatment with H-290/51 (50 mg/kg, p.o.) 30 min before SCI markedly attenuated HSP expression in the spinal cord seen at 5 h. The motor functions of traumatized rats were also improved in the drug treated group. At this time, structural changes in the spinal cord and edema formation were considerable reduced compared to the untreated traumatized rats. Taken together, these observations suggest that (i) oxidative stress participates in HSP response following trauma, and (ii) the antioxidant compound H-290/51 attenuates cellularstress, improves motor functions and induces considerable neuroprotection in the early phase of SCI. Further studies using post-injury treatment with H-290/51 is needed to explore its therapeutic potentials in clinical settings.

Bridge to heart transplantation with the HeartMate device in Gothenburg, Sweden.

BACKGROUND: Patients rapidly deteriorating while waiting for heart transplantation present a major problem. Our strategy for this entity is the HeartMate left ventricular assist device (LVAD) VELVAS, an electrically driven implantable LVAD. Herein we report our initial experience. METHODS: The medical records of all the patients who received HeartMate LVAS at our institution were reviewed. RESULTS: From January 1997 through May 2004, 19 patients received a HeartMate. The mean age was 39 (15 to 61) years and 84% were men. The diagnoses were: dilated cardiomyopathy (n = 8), ischemic heart disease (n = 6), myocarditis (n = 3), congenital heart disease (n = 1), and hypertrophic cardiomyopathy (n = 1). Mean time on LVAD was 113 (10 to 353) days. Ten patients were discharged from the hospital to their homes awaiting transplant or recovery. Three patients showed recovery of heart function and were subsequently weaned from mechanical support. Thirteen patients underwent heart transplantation. Three patients died during LVAD treatment. Major adverse events occurred in nine patients, including severe right heart failure (n = 3), severe bleeding (n = 3), stroke (n = 1), hepatic failure (n = 1), and septicemia (n = 2). Nine of the 13 transplanted patients are alive and well today. CONCLUSION: HeartMate LVAS is a valuable option for patients rapidly deteriorating while awaiting a heart transplant. Our results are comparable with those reported from larger centers.