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Objective: Bilateral chronic high frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) has emerged as an appropriate therapy for patients with advanced Parkinson's disease refractory to medical therapy. Advances in neuroimaging and neurophysiology have led to the development of varied targeting methods for the delivery of this treatment. Intraoperative neurophysiological and clinical monitoring is regarded by many to be mandatory for accurate STN localisation. We have examined efficacy of bilateral STN stimulation using a predominantly magnetic resonance imaging (MRI)-directed technique.Methods: DBS leads were stereotactically implanted into the STN using an MRI directed method, with intraoperative macrostimulation used purely for adjustment. The effects of DBS were evaluated in 16 patients followed up to 12 months, and compared with baseline assessments. Assessments were performed in both off and on medication states, and were based on the Unified Parkinson's Disease Rating Scale (UPDRS) and timed motor tests. Functional status outcomes were examined using the PDQ-39 quality of life questionnaire. A battery of psychometric tests was used to assess cognition.Results: After 12 months, stimulation in the off medication state resulted in significant improvements in Activities of Daily Living and Motor scores (UPDRS parts II and III) by 62% and 61% respectively. Timed motor tests were significantly improved in the off medication state. Motor scores (UPDRS part III) were significantly improved by 40% in the on medication state. Dyskinesias and off duration were significantly reduced and the mean dose of L-dopa equivalents was reduced by half. Psychometric test scores were mostly unchanged or improved. Adverse events were few.Conclusions: An MRI directed targeting method for implantation of DBS leads into the STN can be used safely and effectively, and results are comparable with studies using intraoperative microelectrode neurophysiological targeting. In addition, our method was associated with an efficient use of operating time, and without the necessary costs of microelectrode recording. [ABSTRACT FROM AUTHOR]

Objective: To assess whether a novel 'direct access pathway' (DAP) for the management of high-risk non-ST-elevation acute coronary syndromes (NSTEACS) is safe, results in 'shorter time to intervention and shorter admission times'. This pathway was developed locally to enable London Ambulance Service to rapidly transfer suspected high-risk NSTEACS from the community to our regional heart attack centre for consideration of early angiography. Methods: This is a retrospective case-control analysis of 289 patients comparing patients with high-risk NSTEACS admitted via DAP with age-matched controls from the standard pan-London high-risk ACS pathway (PLP) and the conventional pathway (CP). The primary end point of the study was time from admission to coronary angiography/intervention. Secondary end point was total length of hospital stay. Results: Over a period of 43 months, 101 patients were admitted by DAP, 109 matched patients by PLP and 79 matched patients through CP. Median times from admission to coronary angiography for DAP, PLP and CP were 2.8 (1.5-9), 16.6 (6-50) and 60 (33-116) hours, respectively (p<0.001). Median length of hospital stay for DAP and PLP was similar at 3.0 (2.0-5.0) days in comparison to 5 (3-7) days for CP (p<0.001). Conclusions: DAP resulted in a significant reduction in time to angiography for patients with high-risk NSTEACS when compared to existing pathways. [ABSTRACT FROM AUTHOR]

Objective Longer-term effects of prolonged selective interleukin-1β blockade with canakinumab were evaluated in the largest cohort of cryopyrin-associated periodic syndrome (CAPS) patients studied to date. Methods Adult and paediatric CAPS patients (n=166, including canakinumab-naive and pretreated patients from previous studies) received canakinumab subcutaneously 150 mg or 2 mg/kg (≤40 kg) every 8 weeks for up to 2 years. Response and relapse was assessed using scores for disease activity, skin rash and C-reactive protein (CRP) and/or serum amyloid A (SAA) levels. Results Complete response was achieved in 85 of 109 canakinumab-naive patients (78%; 79/85 patients within 8 days, and five patients between days 10 and 21). Of 141 patients with an available relapse assessment, 90% did not relapse, their CRP/SAA levels normalised (<10 mg/l) by day 8, and remained in the normal range thereafter. Median treatment duration was 414 days (29-687 days). Upward adjustments of dose or frequency were needed in 24.1% patients; mostly children and those with severe CAPS. Predominant adverse events (AE) were infections (65.7%) of mostly mild-to-moderate severity. Serious AE reported in 18 patients (10.8%) were mainly infections and were responsive to standard treatment. The majority of patients (92%) reported having no injection-site reactions and only 8% patients reported mild-to-moderate reactions. Patients receiving vaccination (15%) showed normal immune response. Conclusions Subcutaneous canakinumab 150 mg every 8 weeks was well tolerated and provided substantial disease control in children and adults across all CAPS phenotypes. Higher canakinumab doses in younger patients and more severe CAPS disease were efficacious in achieving complete responses without evidence of increased AE. [ABSTRACT FROM AUTHOR]

Introduction: To better understand, and ultimately prevent, infant/child homicide, it is imperative to more thoroughly elucidate the circumstances and conditions related to such instances. Data were obtained from the US National Violent Death Reporting System (NVDRS) to illuminate circumstances related to homicide among children aged 4 years or less, and to identify demographic groups which may be at increased risk. Methods: The NVDRS is on active surveillance system that provides comprehensive information on all violent deaths that occur within participating states within the US. Standard statistical tests were conducted to determine homicide rates among children ages 0–4 across states that provided data for both 2003 and 2004 (Alaska, Maryland, Massachusetts, New Jersey, Oregon, South Carolina, and Virginia). These data were further used to investigate infant/child homicides by race, gender, and other relevant circumstances (for example, victim-suspect relationship, weapon type, and location of homicide). A Poisson regression model was fitted to the sample data to investigate the multivariate relationship between the infant/child homicide rate and available demographic information. Results: The 2003 homicide rate for children ages 0–4 was 3.0 per 100 000 population. The 2004 homicide rate was 2.5 per 100 000 population. African Americans were 4.2 times as likely as whites to be victims of homicide. Suspects were commonly parents/caregivers. The vast majority of infant/child homicides occurred in houses or apartments, using weapons that include household objects. Conclusion: Homicides of infants and young children are most often committed in the home, by parents/caregivers, using ‘weapons of opportunity’. This suggests that the risk of infant/child homicide is greatest within the primary care giving environment. Moreover, the use of ‘weapons of opportunity’ may be indicative of maladaptive stress responses. Prevention and intervention strategies to reduce infant/child homicide should target the home environment and attend to maladaptive stress responses. [ABSTRACT FROM AUTHOR]

Background and aims: A reliable non-invasive assessment of the severity of diffuse liver disease is much needed. We investigated the utility of hepatic vein transit times (HVTT) for grading and staging diffuse liver disease in a cohort of patients with hepatitis C virus (HCV) infection using an ultrasound microbubble contrast agent as a tracer. Materials and methods: Eighty five untreated patients with biopsy proven HCV induced liver disease were studied prospectively. All were HCV RNA positive on polymerase chain reaction testing. Based on their histological fibrosis (F) and necroinflammatory (NI) scores, untreated patients were divided into mild hepatitis (F &les; 2/6, NI &les; 3/18), moderate/severe hepatitis (3 &les; F <6 or NI &ges; 4), and cirrhosis (F = 6/6) groups. In addition, 20 age matched healthy volunteers were studied. After an overnight fast, a bolus of contrast agent (Levovist) was injected into an antecubital vein and spectral Doppler signals were recorded from both the right and middle hepatic veins for analysis. HYTTs were calculated as the time from injection to a sustained rise in Doppler signal >10% above baseline. The Doppler signals from the carotid artery were also measured in 60 patients and carotid delay times (CDT) calculated as the difference between carotid and hepatic vein arrival times. The earliest HVTT in each patient was used for analysis. Results: Mean (SEM) HVTT for the control, mild hepatitis, moderate/severe hepatitis, and cirrhosis groups showed a monotonic decrease of 38.1 (2.8), 38.8 (2.4), 26.0(2.4), and 15.8 (0.8) seconds, respectively. Mean (SEM) CDT for the control, mild hepatitis, moderate/severe hepatitis, and cirrhosis patients again showed progressive shortening of 30.3 (2.6), 25.9 (2.6), 14.8 (2.1), and 5.6 (1.2) seconds, respectively. There were significant differences between the groups for HVTT (ANOVA, p<0.001) and CDT (ANOVA, p<0.001). There was 100% sensitivity and 80% specificity for diagnosing cirrhosis and 95% sensitivity and 86% specificity for differentiating mild hepatitis from more severe liver disease. Conclusion: We have shown, for the first time, that HVTT using an ultrasound microbubble contrast agent can assess HCV related liver disease with clear differentiation between mild hepatitis and cirrhosis. There were significant differences between these two groups and the moderate/severe hepatitis group. CDT offers no additional benefit or greater differentiation than NYU and can be omitted, thus simplifying this technique. HVTT may complement liver biopsy and may also be a useful alternative for assessment of liver disease in patients who have contraindications to biopsy. [ABSTRACT FROM AUTHOR]

Background: Hepatic steatosis is associated with obesity and type II diabetes. Proton magnetic resonance spectroscopy (¹H MRS) is a non-invasive method for measurement of tissue fat content, including intrahepatocellular lipids (IHCL) and intramyocellular lipids (IMCL). Patients and methods: We used ¹H MRS and whole body magnetic resonance imaging (MRI) to assess the relationship between IHCL accumulation, total body adipose tissue (AT) content/distribution, and IMCL content in 11 subjects with biopsy proven hepatic steatosis and 23 normal volunteers. Results: IHCL signals were detectable in all subjects but were significantly greater in hepatic steatosis (geometric mean (GM) 11.5 (interquartile range (IQR) 7.0-39.0)) than in normal volunteers (GM 2.7 (1QR 0.7-9.3); p = 0.02). In the study group as a whole, IHCL levels were significantly greater in overweight compared with lean subjects (body mass index (BMI) >25 kg/m² (n = 23): GM 7.7 (IQR 4.0-28.6) v BM1 <25 kg/m² (n =11): GM 1.3 (IQR 0.3-3.6; p =0.004)). There was a significant association between IHCL content and indices of overall obesity (expressed as a percentage of body weight) for total body fat (p = 0.001), total subcutaneous AT (p =0.007), and central obesity (subcutaneous abdominal AT (p =0.001) and intra-abdominal AT (p =0.001)), after allowing for sex and age. No correlation between IHCL content and MCI was observed. A significant correlation was observed between serum alanine aminotransferase and liver fat content (r=0.57, p=0.006). Conclusions: Our results suggest that hepatic steatosis appears to be closely related to body adiposity, especially central obesity. MRS may be a useful method for monitoring IHCL in future interventional studies. [ABSTRACT FROM AUTHOR]

Objective: To assess the safety and effectiveness of nurse led elective cardioversion of atrial fibrillation under sedation. Design: Prospective, longitudinal study. Setting: Cardiac catheterisation laboratory and recovery area of a district general hospital. Patients: 300 patients referred for elective cardioversion of persistent atrial fibrillation. Interventions: Pre-procedure evaluations (history, physical examination, blood tests), consent, sedation administration, cardioversions, and post-procedure monitoring until discharge by advanced life support certified coronary care unit nurses trained in the techniques. A doctor was immediately available if required but not present. Main outcome measures: Success rates at discharge and at six weeks, energy delivered, number of shocks, dose of sedation, immediate, 24, and 48 hour patient perceptions, complications, waiting times, and cost effectiveness. Results: Cardioversion success rate was 87% at discharge and 48% at six weeks. Mean (SD) cumulative energy was 497 (282) J and number of shocks 1.6 (0.8). Mean (SD) dose of sedation was 23 (9) mg intravenous diazepam. No patient required reversal of sedation, airway support, or medical intervention. Ninety eight per cent of patients had no pain or recall of the procedure. Four patients who were adequately anticoagulated experienced embolic phenomena. Ninety eight per cent of patients would repeat the procedure if necessary. Without requirement for a physician or anaesthetist, waiting times for elective cardioversion fell from three months to under four weeks. There was a significant reduction in the estimated cost of the procedure from £337 with general anaesthesia to £130 with nurse led sedation and cardioversion (p < 0.001). Conclusion: With appropriate training, a nurse led cardioversion service with sedation is safe, effective, well tolerated, and cost efficient. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate optical coherence tomographic elastography as a method for assessing the elastic properties of atherosclerotic plaque and the parameters that influence interpretation.Methods: Phantoms and aorta were examined in vitro to quantify speckle modulation and measure the displacement and strain maps. A correlation method was used as a speckle tracking technique for measuring axial and lateral displacement vectors and calculation of strain maps. The influence of correlation kernel size on accuracy of the method was evaluated.Results: In terms of a percentage error between calculated and measured displacements, the best results for phantoms were obtained with a 41 x 41 kernel (1.88% error). For both phantom and aorta images, it was found that, with the increasing size of cross correlation kernel, the axial and lateral displacement maps are less noisy and the displacement vectors are more clearly defined. However, the large kernels tend to average out the differences in displacements of small particles in phantoms and decrease the ability of speckle tracking to make microstructural assessments. Therefore, it is important to select kernel size carefully, based on the image features.Conclusions: Optical tomographic elastography can be used to assess the microstructural properties of atherosclerotic tissue at micrometre scale resolution, but preselected analysis criteria must be understood in a critical interpretation of the results. [ABSTRACT FROM AUTHOR]

Background and aim: Fatigue is the commonest symptom in primary biliary cirrhosis (PBC), affecting individuals at all stages of disease. The pathogenesis of fatigue in PBC is unknown although rat models suggest a central nervous system (CNS) cause. We examined the hypothesis that a CNS abnormality related to cholestasis, rather than cirrhosis per se, underlies this symptom. Patients and methods: Fourteen patients with precirrhotic PBC (stage I-II disease), four patients with stage III-IV PBC, and 11 healthy women were studied using cerebral magnetisation contrast imaging and proton magnetic resonance spectroscopy (MRS). Results: The globus pallidus magnetisation transfer ratio (MTR), a quantifiable tissue characteristic that may be abnormal in the presence of normal magnetic resonance imaging, was significantly reduced in precirrhotic PBC patients compared with healthy controls. These measurements correlated with blood manganese levels and were more abnormal in the more fatigued subjects. There were no differences in MRS measurements between the three study groups, suggesting that the abnormal MTR was not related to hepatic encephalopathy. Conclusion: This study suggests that impairments in liver function in PBC may adversely affect the brain long before the development of cirrhosis and hepatic encephalopathy, possibly as a result of altered manganese homeostasis within the CNS. [ABSTRACT FROM AUTHOR]

Background: A previous pilot study showed that early arrival time of a microbubble in a hepatic vein is a sensitive indicator of cirrhosis. Aim: To see if this index can also grade diffuse liver disease. Patients: Thirty nine fasted patients with histologically characterised disease were studied prospectively. Nine patients had no evidence of liver fibrosis, 10 had fibrosis without cirrhosis, and 20 had cirrhosis (five Child's A, seven Child's B, and eight Child's C). Methods: Bolus injections of a microbubble (Levovist; Schering, Berlin) were given intravenously, followed by a saline flush. Time intensity curves of hepatic vein and carotid artery spectral Doppler signals were analysed. Hepatic vein transit time (HVTT) was calculated as the time after injection at which a sustained signal increase >10% of baseline was seen. Carotid delay time (CDT) was calculated as the difference between carotid and hepatic vein enhancement. Results: Diagnostic studies were achieved in 38/39 subjects. Both HVTT and CDT became consistently shorter with worsening disease, as follows (means (SD)): HVTT: no fibrosis 44 (25) s, fibrosis 26 (8) s, Child's A 21 (1) s, Child's B 16 (3) s, and Child's C 16 (2) s; CDT: no fibrosis 31 (29) s, fibrosis 14 (6) s, Child's A 8 (1) s, Child's B 4 (4) s, and Child's C 3 (3) s. These differences were highly significant (p<0.001, ANOVA comparison). A HVTT <24 s and a CDT <10 s were 100% sensitive for cirrhosis (20/20 and 18/18, respectively) but not completely specific: 2/8 subjects with fibrosis had CDT values <10 s and 3/9 had HVTT <24 s. Conclusion: This minimally invasive test shows promise not only in diagnosing cirrhosis but also in assessing disease severity. [ABSTRACT FROM AUTHOR]

Van Buchem disease is an autosomal recessive skeletal dysplasia characterised by generalised bone overgrowth, predominantly in the skull and mandible. Clinical complications including facial nerve palsy, optic atrophy, and impaired hearing occur in most patients. These features are very similar to those of sclerosteosis and the two conditions are only differentiated by the hand malformations and the tall stature appearing in sclerosteosis. Using an extended Dutch inbred van Buchem family and two inbred sclerosteosis families, we mapped both disease genes to the same region on chromosome 17q12-q21, supporting the hypothesis that van Buchem disease and sclerosteosis are caused by mutations in the same gene. In a previous study, we positionally cloned a novel gene, called SOST, from the linkage interval and identified three different, homozygous mutations in the SOST gene in sclerosteosis patients leading to loss of function of the underlying protein. The present study focuses on the identification of a 52 kb deletion in all patients from the van Buchem family. The deletion, which results from a homologous recombination between A/u sequences, starts approximately 35 kb downstream of the SOST gene. Since no evidence was found for the presence of a gene within the deleted region, we hypothesise that the presence of the deletion leads to a down regulation of the transcription of the SOST gene by a cis regulatory action or a position effect. [ABSTRACT FROM AUTHOR]

Objectives: This study examined the scanpaths of patients with homonymous hemianopia while viewing naturalistic pictures in their original and also spatially filtered forms. Features of their scanpaths with respect to various saccade and fixation parameters were examined to determine whether they develop compensatory eye movement strategies. The effects of various lesion parameters including location, size, and age on the evolution of such strategies were considered.Methods: Eye movements of eight patients with homonymous hemianopia (four left, four right), but lacking neglect, were recorded while they viewed 22 images of real scenes, and they were compared with the eye movements of eight age matched controls. Subjects viewed each image for 3 seconds, initially in a spatially filtered form in which much of the semantic content had been removed, and then in their unfiltered, original form.Results: Patients differed significantly from controls in various fixation and saccade parameters. For fixation parameters patients with hemianopia fixated different spatial positions from controls, made more fixations which were more widely distributed and of shorter duration than controls, and spent a greater proportion of their total fixation time in the area corresponding to their blind hemifield. They did not make significantly more refixations than controls. For saccade parameters patients made more saccades into their blind hemifield, these saccades having shorter latencies and shorter amplitudes than those made into their seeing field, and had longer scanpaths than control subjects. The amplitude of their first saccade was longer than that of controls although its direction did not correlate simply with the side of the field defect. Their mean saccade amplitude was similar to that of controls. Filtering out high spatial frequencies within images seemed to accentuate the described differences between eye movement characteristics of hemianopes and controls. Scanpath differences correlated with increasing age but not location or size of lesions causing the hemianopia.Conclusion: Various features of scanpaths produced by hemianopes were different from normal subjects. These differences correlated with lesion age and may reflect the evolution of a compensatory eye movement strategy. [ABSTRACT FROM AUTHOR]

Aims: To study early neonatal metabolic adaptation in a hospital population of neonates in Nepal.Methods: A cross sectional study was made of 578 neonates, 0 to 48 hours after birth, in the main maternity hospital in Kathmandu. The following clinical and nutritional variables were assessed: concentrations and age profiles of blood glucose, hydroxybutyrate, lactate, pyruvate, free fatty acids (FFA) and glycerol; associations between alternative fuel levels and hypoglycaemia; and regression of possible risk factors for ketone availability.Results: Risk factors for impaired metabolic adaptation were common, especially low birthweight (32%), feeding delays, and cold stress. Blood glucose and ketones rose with age, but important age effects were also found for risk factors like hypothermia, thyroid hormone activities, and feeding practices. Alternative fuel concentrations, except FFA, were significantly reduced in infants with moderate hypoglycaemia during the first 48 hours after birth. Unlike earlier studies, small for gestational age (SGA) infants had significantly higher hydroxybutyrate:glucose ratios which suggested counter regulatory ketogenesis. Hypoglycaemic infants were not hyperinsulinaemic. Regression analysis showed risk factors for impaired counter regulation which included male and large infants, hypothermia, and poorer infant thyroid function. SGA infants and those whose mothers had received no antenatal care had increased counter regulation.Conclusions: Alternative fuels are important in the metabolic assessment of neonates, and they might provide effective cerebral metabolism even during moderate hypoglycaemia. Hypoglycaemic infants generally had lower concentrations of alternative fuels through either reduced availability or increased consumption. SGA and post term infants increased counter regulatory ketogenesis with early neonatal hypoglycaemia, but hypothermia, male gender, and low infant T4 were associated with impaired counter regulation after birth. [ABSTRACT FROM AUTHOR]

Aims: To measure the prevalence of hypoglycaemia among newborn infants in Nepal, where classic risk factors prevail, and to evaluate their importance.Methods: A cross sectional study was done of 578 term newborn infants aged 0 to 48 hours on the postnatal wards of a government maternity hospital in Kathmandu, with unmatched case-control analysis of risk factors for moderate hypoglycaemia (less than 2.0 mmol /l).Results: Two hundred and thirty eight (41%) newborn infants had mild (less than 2.6 mmol/l) and 66 (11%) moderate hypoglycaemia. Significant independent risk factors for moderate hypoglycaemia included postmaturity (OR 2.62), birthweight under 2.5 kg (OR 2.11), small head size (OR 0.59), infant haemoglobin >210 g/l (OR 2.77), and raised maternal thyroid stimulating hormone (TSH) (OR 3.08). Feeding delay increased the risk of hypoglycaemia at age 12-24 hours (OR 4.09). Disproportionality affected the risk of moderate hypoglycaemia: lower with increasing ponderal index (OR 0.29), higher as the head circumference to birthweight ratio increased (OR 1.41). Regression expressing blood glucose concentration as a continuous variable revealed associations with infant haemoglobin (negative) and maternal haemoglobin (positive), but no other textbook risk factors.Conclusions: Neonatal hypoglycaemia is more common in a developing country, but may not be a clinical problem unless all fuel availability is reduced. Some textbook risk factors, such as hypothermia, disappear after controlling for confounding variables. Early feeding could reduce moderate hypoglycaemia in the second 12 hours of life. The clinical significance of raised maternal TSH and maternal anaemia as prenatal risk factors requires further research. [ABSTRACT FROM AUTHOR]

AIMS--To investigate the prevalence of Helicobacter pylori in the saliva of patients infected with this bacterium. METHODS--A novel polymerase chain reaction (PCR) assay was developed to detect H pylori in saliva and gastric biopsy specimens from patients undergoing endoscopy. RESULTS--Our PCR assay amplified a 417 base pair fragment of DNA from all 21 DNAs derived from H pylori clinical isolates but did not amplify DNA from 23 non-H pylori strains. Sixty three frozen gastric biopsy and 56 saliva specimens were tested. H pylori specific DNA was detected by PCR in all 39 culture positive biopsy specimens and was also identified from another seven biopsy specimens which were negative by culture but positive by histology. H pylori specific DNA was identified by PCR in saliva specimens from 30 (75%) of 40 patients with H pylori infection demonstrated by culture or histological examination, or both, and in three patients without H pylori infection in the stomach. CONCLUSION--The results indicate that the oral cavity harbours H pylori and may be the source of infection and transmission. [ABSTRACT FROM PUBLISHER]

A silver enhanced, gold labelled, immunosorbent assay (SEGLISA) for the detection of IgG antibodies to the rubella virus in human serum was developed. Pre-coated microtitre wells are used as the immobilised base of rubella antigens on to which any rubella antibodies from patient samples will bind. This antigen/antibody complex is then visualised firstly by gold labelled anti-immunoglobulin G, which binds to any human IgG that may be present, and then by silver amplification, resulting in a black permanent deposit on the microtitre well surface. Patient samples (n = 121) were screened using a commercially available enzyme linked immunosorbent assay (ELISA) and an equivalent SEGLISA. Results were comparable but the SEGLISA does not have the disadvantages associated with enzyme labels. The silver deposit may also be read visually or the dried plate may be stored for future reference. [ABSTRACT FROM PUBLISHER]

To determine the extent of intrapartum intervention received by primigravidas. Cross sectional survey of NHS hospitals in the UK. One hundred and one randomly selected hospital maternity units. Forty consecutive primigravid women, judged to be at low risk at the start of labour, in each hospital. Seven groups of interventions or monitoring procedures were identified from the first, second, and third stages of labour: fetal monitoring, vaginal examinations, artificial rupture of membranes, augmentation of labour, pain relief, type of delivery, and episiotomy. Data were collected during 1993. Ninety eight hospitals took part in the study and data were collected on 3160 low risk primigravidas. Seventy four per cent of these women had continuous cardiotocography. The proportion of women having restrictive or invasive fetal monitoring showed appreciable geographical variation for both the first and second stages of labour. Using the criterion of a vaginal examination every four hours and allowing for the length of each woman's labour, 72% had more vaginal examinations than expected; there was a significant geographical variation in the number of women receiving more than five examinations. Fifty three per cent had artificial rupture of membranes; the procedure was performed over a wide range of cervical dilatations (0 cm-10 cm). Thirty eight per cent of labours were augmented, most commonly by intravenous syntocinon; the procedure showed significant geographical variation. Twenty eight per cent had a spinal block or epidural analgesia for the relief of pain; this intervention varied by geographical region only for the second stage of labour. Over one quarter of the women required instrumental delivery. Forty six per cent had an episiotomy; the frequency of this intervention varied substantially by region. There were no infant deaths. Twelve babies were recorded at birth as having a congenital anomaly. The rates of several interventions seem high for this low risk group and there was substantial geographical variation in the use of six interventions. Clinical trials are needed to evaluate the optimum criteria for using these interventions from which guidelines should be drawn up by local groups and the Royal College. [ABSTRACT FROM AUTHOR]

Aims: To compare two cotside methods of blood glucose measurement (HemoCue and Reflolux II) against a standard laboratory method for the detection of neonatal hypoglycaemia in a developing country maternity hospital where hypoglycaemia is common.Methods: 94 newborn infants and 75 of their mothers had blood glucose assessed on the same venous sample using three different methods in the Special Care Baby Unit and postnatal wards, Prasuti Griha Maternity Hospital, Kathmandu, Nepal: HemoCue and Reflolux II at the cotside; Roche Ultimate glucose oxidase method (GOM) in the laboratory.Results: The mean (SD) values for blood glucose in newborn infants were GOM 2.5 (1.1) mmol/l; Reflolux II 2.1 (0.9); and HemoCue 4.2 (1.2). For mothers the values were GOM 5.3 (1.2) mmol/l; Reflolux II 3.6 (1.2); and HemoCue 5.6 (1.0). Bland-Altman plots showed that Reflolux II consistently underreads GOM blood glucose in neonates by 0.5 mmol/l (SD 0.7) and that HemoCue overreads glucose by 1.7 mmol/l (SD 0.8). For the detection of hypoglycaemia (< 2.0 mmol/l), Reflolux II achieved a sensitivity of 83%, a specificity of 62%, and a likelihood ratio of 2.2. HemoCue produced a sensitivity of 0% and a specificity of 100% using measured values. If 2.0 mmol were subtracted from all Hemocue values this rose to 81% and 68% and a likelihood ratio of 2.5.Conclusion: Although more accurate than Reflolux II for the measurement of blood glucose in mothers, HemoCue overreads glucose concentrations in neonates and is therefore potentially dangerous as a screening method for neonatal hypoglycaemia. Reflolux II is useful as a screening method for high risk infants (low birthweight, post-term) and could achieve a post-test probability of detecting hypoglycaemia in a high risk setting like Nepal of 50-60%. [ABSTRACT FROM AUTHOR]

OBJECTIVE--To assess the outcome of percutaneous balloon dilatation of the mitral valve in critically ill young patients with intractable heart failure. DESIGN--Retrospective analysis of all such patients presenting over a period of 4 years. PATIENTS--Of 432 consecutive patients undergoing percutaneous balloon dilatation of the mitral valve, 12 (mean age 29 years) with intractable heart failure were identified. Nine had severe pulmonary oedema and three had pulmonary oedema with severe right heart failure and hypotension. Three patients were pregnant and three required mechanical; ventilatory support. PROCEDURE--Percutaneous balloon dilatation of the mitral valve was performed using the Inoue balloon technique. The procedure was shortened by excluding full right study, cardiac output measurement, and left ventriculography. The mitral valve morphology and mitral valve area were determined before and after percutaneous balloon dilatation using cross sectional Doppler echocardiography. RESULTS--The procedure was technically successful in all patients. The mean (SD) echocardiographic value of the mitral valve area increased from 0.7 (0.1) to 1.4 (0.2) cm2 with a concomitant reduction in pulmonary artery systolic pressure (Doppler) from 81 (17) to 50 (7) mm Hg. There was a significant clinical improvement in all patients. The mean (range) fluoroscopy time for the procedure was 6.9 (1.7-14.1) min. During follow up (mean 10 months) nine patients were in New York Heart Association (NYHA) functional class I, one was in class II, one under NYHA elective mitral valve replacement, and one, who refused elective surgery, died suddenly at home. CONCLUSION--Percutaneous balloon dilatation of the mitral valve can be performed as a life saving procedure in critically ill patients with mitral stenosis, as even a modest increase in valve area in these patients produces gratifying clinical improvement. [ABSTRACT FROM PUBLISHER]

OBJECTIVE--To determine the effects of a small dose of beta blocker on neurohumoral and cardiopulmonary responses after cardiac transplantation. BACKGROUND--Cardiac transplant recipients have a reduced exercise capacity and abnormal cardiovascular responses to exercise. The sympathoadrenal response to exercise has been shown to be abnormal with high venous noradrenaline. The effect of beta blockade on these neurohumoral mechanisms has not been defined. METHODS--10 non-rejecting cardiac transplant recipients were studied. Patients carried out graded exercise to a symptom limited maximum. Blood samples were taken during exercise. Concentrations of noradrenaline, adrenaline, and atrial natriuretic peptide and plasma renin activity were measured. The next day, the exercise and sampling procedure were repeated after an oral dose of propranolol (40 mg). RESULTS--Patients tolerated exercise poorly after beta blockade, which was reflected in the maximum workload reached. Heart rate and blood pressure were significantly higher at rest and during exercise before beta blockade. Although there was no significant difference when resting, mean (SEM) noradrenaline concentrations during peak exercise were higher after beta blockade (16.2 (2) v 23.6 (2.9) nmol/l, p = 0.001). Adrenaline concentrations at peak exercise were also greater after beta blockade (0.89 (0.31) v 1.18 (0.38) nmol/l, p = 0.055). Atrial natriuretic peptide concentrations tended to be higher after beta blockade (118.75 (50.2) v 169.79 (39.3) pmol/l, p = 0.36). There was no significant change in plasma renin activity. CONCLUSIONS--A small oral dose of a competitive beta blocker such as propranolol has an adverse effect on exercise tolerance and cardiovascular response to exercise in cardiac transplant recipients. There are also increased concentrations of circulating noradrenaline and therefore, sympathetic activity during exercise. beta blockers should be used with caution in cardiac transplant recipients. [ABSTRACT FROM PUBLISHER]

A non-directive programme of prenatal counselling was used during a four year period. Forty-three couples at risk for having a baby with a haemoglobinopathy were identified. Prenatal diagnosis was offered in 19 pregnancies to 14 couples at risk of having a baby with sickle cell anaemia and in two pregnancies in two couples at risk of a baby with beta thalassaemia major, who presented before the 18th week of pregnancy. Six couples at risk for sickle cell anaemia accepted prenatal diagnosis in 10 pregnancies, as did both couples at risk for thalassaemia. Couples who were eligible for prenatal diagnosis but refused it tended not to have been informed about sickle cell disease before counselling, one partner was more frequently absent at the time of the initial counselling session, or they either had no children with sickle cell disease or the children were not severely affected. Other factors influencing their decision included a poor obstetric history and rejection of abortion, mainly on moral grounds. The approximately 50% uptake of prenatal diagnosis in this initial study highlights the complex issues involved. Our experience indicates that with systematic screening and counselling in the antenatal clinic, and with increased awareness of the haemoglobinopathies, couples at risk will be in a better position to make informed decisions. [ABSTRACT FROM PUBLISHER]

AIM: To assess whether bile duct loss is associated with the bile duct damage induced by chronic hepatitis C. METHODS: Sections were examined from 171 liver biopsy specimens from patients with chronic hepatitis C, 98 biopsy specimens from patients with chronic hepatitis B, 25 postmortem specimens from patients with no evidence of liver disease, and 23 patients who underwent protocol liver biopsy at the time of cholecystectomy. RESULTS: The bile duct:portal tract ratio for the hepatitis C group was 0.89, for the hepatitis B group was 0.93 and for the two control groups was 0.96 and 0.90, respectively. The ratio was lower in the hepatitis C group than in the other three. In no case of chronic hepatitis C was the ratio less than 0.60. In the hepatitis C group greater bile duct loss was seen in cirrhotic patients. CONCLUSIONS: Hepatitis C is associated with bile duct loss and this was related to the stage of the disease. However, in the cases studied this did not reach what is generally considered to be significant (that is, greater than 50% of portal tracts lacking bile ducts). This does not preclude a contributory effect of hepatitis C to bile duct loss in the presence of other risk factors, especially in liver transplant recipients. [ABSTRACT FROM PUBLISHER]

The cases are reported of three off road cyclists with isolated soft tissue injuries to the right lower leg, caused by the chain ring as they struggled to release their feet from clipless pedals. Correct adjustment of the pedals to facilitate quick release of the feet is required to prevent such injuries. [ABSTRACT FROM AUTHOR]

This article focuses on a study that compares poorer short term outcome in indo-asians and Caucasians after percutaneous coronary intervention (PCI) for ethnicity as an independent risk factor. Despite the complex nature of this patient group there is a low incidence of tropinin elevation and myocardial necrosis following PCI. Coronary artery disease tends to be more extensive and diffuse in Indo-Asians (IA) as compared with Caucasians. There are, however, few data relating to ethnicity and outcome after revoscularisation. Ethnicity in relation to lAs emerged as an independent risk factor for poor short term outcome following PCI.

Reports on a case of recurrent ectasia following deep lamellar keratoplasty supported by clinical and histological evidence. Development of a persistent central epithelial defect after surgery, which later became infected; Uniocular visual acuity; Advantages of deep lamellar keratoplasty over penetrating keratoplasty.

Focuses on the importance of molecular testing in dominant optic atrophy. Definition of juvenile onset dominant optic atrophy; Enumeration of clinical features; Occurrence of dominant optic atrophy due to mutations in genes.

Injecting drug users frequently use accident and emergency (A&E) departments to access emergency care for local and systemic infections. Clostridium novyi type A is a bacterium that has recently been associated with a number of fatalities among drug injecting addicts. The clinical course is described of a patient who attended an A&E department with septicaemia who was found at postmortem examination to have been infected with Clostridium novyi type A. Doctors working in A&E departments should be aware of the existence of this infection and be vigilant when treating injecting drug users with localised infection. [ABSTRACT FROM AUTHOR]

Objective To assess (1) agreement between the ultrasonic cardiac output monitor (USCOM) 1A device for measurement of cardiac output in newborn infants and conventional echocardiography (ECHO), (2) repeatability of USCOM measurements and (3) agreement between novice and expert users of the USCOM. Design A prospective observational study. Setting The Neonatal Unit at the Royal Children's Hospital, Melbourne, Australia. Patients 56 term and near-term infants, with no evidence of structural or functional cardiovascular disease, or haemodynamic shunts. Measurements Agreement between ECHO and USCOM was assessed by paired measurements of ventricular outputs by a single experienced user. Repeatability was assessed using five repeated measurements in 10 infants. Agreement between five novices and one expert user was assessed by paired USCOM measurements over 30 training measurements. Results Agreement between USCOM and ECHO for left ventricular output (LVO) was (bias, ±limits of agreement, mean % error): 14, ±108 ml/kg/min, 43%, and for right ventricular output (RVO): -59, ±160, ml/kg/min, 57%. Intra-observer repeatability was 6.7% for USCOM LVO and 3.6% for ECHO LVO. After five training measurements, the mean difference between USCOM measures of LVO by novice and expert users was less than 50 ml/kg/min, but with variability. Conclusions Repeatability of USCOM measures is high in newborn infants. New users can be trained quickly, but with high inter-user variability. Agreement between USCOM and conventional ECHO is broad, and worse for RVO and LVO. Further studies are required to assess the ability of the device to detect clinically significant changes in infant cardiac output. [ABSTRACT FROM AUTHOR]

Introduction Non-alcoholic fatty liver disease (NAFLD) is increasingly common with a prevalence of between 20% and 34% in Europe and the US. There is a close association between NAFLD and other features of the metabolic syndrome such as insulin resistance, hypertension and obesity. We investigated liver health in patients with diabetes, and the effect of lifestyle interventions on liver health in newly diagnosed type 2 diabetics. Methods Patients within 5–8 months of diagnosis of diabetes were identified from four centres in the South West of England. All participants received usual care for patients with diabetes. Patients were randomised to usual care alone (UC), additional dietary advice (D) or additional dietary and exercise advice (D&E). LFTs were measured at baseline and twelve months. Results Median age of participants was 61 years, 36% were female. Alcohol intake was modest and did not differ significantly between groups. Modest reductions in BMI and insulin resistance were seen in groups D and D&E: these were not significant. There was no change in blood pressure. At baseline 24 of 424 patients (5.6%) had any abnormality in liver function. At twelve months this was 15 of 212 patients (7.1%). Increased prevalence was seen in all groups except D. Transaminase levels followed the same trend with regard to prevalence at baseline (2.6%) and 12 months (3.7%). AST:ALT ratio (AAR) increased over twelve months with Pearson correlation of 0.92. In patients with abnormal transaminases non-invasive assessment of fibrosis (NAFLD fibrosis score) demonstrated that 20% of patients were at risk of advanced fibrosis at baseline, climbing to 80% at twelve months, without differences between groups. This is 0.5% and 3% of all participants at baseline and twelve months respectively. Conclusion In newly diagnosed diabetes abnormalities of liver function persist in the first year of diagnosis regardless of lifestyle intervention. Estimation of fibrosis in a subgroup of patients demonstrated increased prevalence of advanced fibrosis over twelve months. This is consistent with rising AAR over the same period for the whole group. Longer-term follow up of these patients is required, but initial data are similar to cohorts described elsewhere in the literature, and reflect a significant risk of liver disease in patients with type 2 diabetes. [ABSTRACT FROM PUBLISHER]

Introduction Hepatic encephalopathy (HE) pathogenesis is related to gut microbial products, which lead to deranged cerebral bioenergetics. Biofluid MR spectroscopy (MRS) can be used to determine changes in bioenergetics, gut microbial products, amino acid and lipid metabolites. Lactulose is used as a first-line HE Rx despite a poor evidence basis. Aim To evaluate the clinical and metabolic consequences of lactulose withdrawal in HE. Method Patients with cirrhosis on lactulose for precipitated HE underwent cognitive testing with inhibitory control (ICT), urine and serum collection for MRS and inflammatory markers while on lactulose. Lactulose was then withdrawn and patients followed for 30 days with visits at day 2, 14 and 30; ICT, serum and urine testing were repeated at every visit. Relapse of HE was defined clinically. Multivariate analysis of urine and serum metabolites involved principal components analysis (PCA) and partial least squares discriminant analysis (PLS-DA). Univariate analysis was applied to hypothesis-driven metabolites, multivariate-driven metabolites and inflammatory marker concentrations. Results 7 cirrhotic men (age 53±7 years, 5 HCV, 2 alcohol) on lactulose for 6±5 months for precipitated HE (5 GI bleed, 2 infections) were included. Three patients clinically relapsed 38±6 days post-withdrawal; all 3 had >15 ICT lures while on lactulose. None of those who scored <15 ICT lures on lactulose relapsed. Lure increase OR, 2.5 (CI: 1.7 to 3.6) predicted relapse. Using ICT lures >15 as a cut-off for HE relapse, MRS distinguished with a sensitivity and specificity of 70.0%/63.6% using urine and 100%/100% using serum on PLS-DA. Urine PLS-DA: In relapsers, urine TMAO was reduced indicating altered gut bacterial metabolism while malonic acid and citrate were higher demonstrating impaired energetics. Glycine and phenylalanine, associated with false neuro-transmitters, were also increased in relapsers along with creatinine. Serum PLS-DA: Relapsers had higher choline and its metabolite, dimethylglycine levels which is associated with extrusion of choline after astrocyte swelling in HE as well as higher levels of lipids. Univariate analysis confirmed that relapsers had lower TMAO (p=0.00280) and higher choline (p=0.0414), LDL (0.0265) and creatinine (p=0.00970). Inflammation was depressed in relapsers compared to others evidenced by decreased endotoxin (p=0.03), IFN-γ (p=0.045), IL-4 (0.0002) and TNF-α (p=0.0013) suggesting a compensatory anti-inflammatory response syndrome. Conclusion HE relapse post-lactulose withdrawal is associated with derangements in bioenergetics, amino-acid, lipid and gut microbial metabolism as well as depression of the inflammatory response. [ABSTRACT FROM PUBLISHER]

Objective This project aims to: (1) describe the frequency of news coverage in mass media related to the National Institute for Health and Clinical Excellence (NICE) draft or final guidance; (2) analyse the types of evidence and sources of information that was quoted in the news; (3) compare whether the patterns of coverage differ between media. Design A survey of news articles related to decisions made by NICE's Health Technology Appraisal committees was conducted. Relevant news articles were retrieved from websites of major UK news media. Inclusion criteria were: (1) news articles related to specific NICE decision(s); (2) articles were written by a reporter/writer/editor of the news media. Articles that mentioned NICE for other reasons, columns and readers' letters were excluded. Setting Major UK news media, including national newspapers and news channels. Samples News articles published during 2007–2008 in 13 different sources of media including tabloids (Daily Express, Daily Mail, News of the World, The Mirror, The Sun), broadsheets (Independent, Guardian, The Telegraph, The Times) and news channels (BBC, ITN, Sky News and Reuters). Main outcome measure The following data were collected by one author and checked by another: nature of guidance (disease area; positive or negative recommendation), use of generic or brand name and source/type of evidence that was quoted. Descriptive statistics were compiled and comparisons between types/sources of news media were made using χ test. Results 329 articles were included. BBC, Daily Mail and The Telegraph published more than 50 articles related to health technology appraisal whereas ITN and News of the World published less than 10 articles during the 2-year period assessed. Two-thirds (220/329) of the articles were related to negative recommendations. There was significant difference in the proportion of articles relating to negative recommendations between individual sources of media (p=0.001) but not between types of media (p=0.286). Cancer (33%), neurology–mainly Alzheimer's disease (22%), ophthalmology (13%) and rheumatology (10%) were most frequently covered areas. 58% (192/329) of the articles quoted only brand names without mentioning generic names of the drugs. Approximately 50% of articles included statements of effectiveness without referring to the source of evidence and another 40% did not describe clinical effectiveness. 24% of articles did not mention drug costs or cost-effectiveness. Conclusion NICE decisions on new drugs, particularly negative recommendations, attracted significant media attention but the coverage and contents varied substantially between individual sources. [ABSTRACT FROM AUTHOR]

Introduction There is increasing interest in the development of imaging-based non-invasive markers for the assessment of chronic liver disease severity. Contrast enhanced ultrasound uses microbubbles as kinetic tracers to assess liver disease severity by exploiting the intra- and extra-hepatic haemodynamic changes accompanying fibrosis and cirrhosis. Transit times of a peripherally administered microbubble bolus are reduced with increasing disease severity. Transit times have previously been calculated to include intra- and extra- hepatic components (the hepatic vein transit time, HVTT) or just the intra-hepatic component (hepatic transit time, HTT), but diagnostic accuracy has not been compared directly. Aim The aims of this study were: 1. to compare the diagnostic accuracy of HVTT and HTT in gauging the severity of chronic hepatitis C (CHC) and 2. to assess the inter- and intra-observer reliability of the microbubble technique. Method 75 patients with biopsy-proven CHC were studied, staged using the Ishak system. Recordings of Doppler US scans performed using the microbubble contrast agent SonoVueTM, were retrospectively analysed by two independent observers, blinded to clinical data, to determine the HVTT, defined as the time taken for the microbubble to travel from the antecubital vein to the hepatic vein, and the HTT, defined as the difference between the hepatic vein arrival time and the hepatic artery arrival time. Each patient had two recordings (with separate microbubble injections) at a 10 min interval. Diagnostic accuracy was assessed using the area under the receiver operator characteristic (AUROC) curve. Inter- and intra- observer reliability and inter-injection reliability were assessed using the intraclass correlation coefficient (ICC). Results 35 patients had mild fibrosis (stage 0–2), 23 had moderate-to-severe fibrosis (stage 3–4) and 17 had cirrhosis (stage 5–6). The diagnostic accuracy (95% CI) of HTT and HVTT for the diagnosis of cirrhosis (stage>4) were 0.78 (0.64–0.92) and 0.71 (0.55–0.86). Diagnostic accuracy (95% CI) of HTT and HVTT for the diagnosis of fibrosis stage >2 were 0.75 (0.65–0.86) and 0.71 (0.59–0.83). Inter-observer reliability (95% CI) for HTT and HVTT were 0.92 (0.87–0.95) and 0.94 (0.91–0.97). Intra-observer reliability for HTT and HVTT were 0.98 (0.97–0.99) and 0.99 (0.98–0.99); inter-recording reliability were0.97 (0.96–0.98) and 0.97 (0.95–0.98) respectively. Conclusion HTT is more accurate than HVTT for the diagnosis of cirrhosis and moderate-to-severe fibrosis, while the reliability both of repeated recordings and of operators' assessment of recordings was very high. HTT reflects the intra-hepatic haemodynamic changes seen in more advanced chronic liver disease accounting for shorter transit times. [ABSTRACT FROM PUBLISHER]

Purpose To develop, optimize and assess the clinical performance of a method for visualizing intracranial stents and their relationships to the host vasculature. Materials and methods Cone beam CT (CBCT) was performed using a flat panel detector angiography system. Datasets were reconstructed from 620 projection images acquired over a 200° arc (rotation time 20.7 s) at 80 kVp and a total of 260 mAs. To maximize spatial resolution, projection images were obtained using a small detector format (22 cm) and reconstructions were performed without pixel binning. A contrast injection protocol was optimized in a porcine model for balance between stent visualization host vessel opacification. Three different intracranial stents were deployed in the internal maxillary arteries of two Yorkshire swine. Selective CBCT angiography was performed at contrast concentrations between 10 and 30% (Iopamidol 51%, by volume in normal saline) and flow rates between 0.5 and 3.5 ml/s. The CBCT datasets were reviewed and the optimal combination of parameters was used for clinical testing. The clinical study was approved by our institutional review board. 57 CBCT examinations of implanted neurovascular stents were performed in 55 patients undergoing cerebral angiography. Two patients each received stents in two locations during treatments of separate aneurysms. Five cases were excluded from the study: four due to the use of balloon mounted stents that are visible with standard angiography and one due to failed contrast injection. The majority of included cases (46/52) were stents placed for treatment of intracranial aneurysms. Stents were placed in six cases to treat dissecting vertebral artery aneurysm, vertebrobasilar insufficiency, acute ischemic stroke and severe middle cerebral artery stenosis. For clinical evaluation, the CBCT dataset was reconstructed with a 512 matrix covering a cubic FOV of 34.4 mm in each dimension (67 μm isotropic voxels). Images were assessed through blinded review by three interventional neuroradiologists using a structured questionnaire. Stent and host vessel visibility were rated on scales of 1–3, and the ability to assess stent apposition was rated ‘yes’ or ‘no’. Results The optimal injection protocol for carotid artery injections was 20% contrast at a flow rate of 3.0 ml/s. The flow rate was reduced to 2.0 ml/s for clinical vertebral artery injections. In 96.1% of cases (50/52), all reviewers rated visualization as sufficient to delineate the configuration and position of each stent (score≥2). In 100% of these cases, all reviewers agreed that the studies were sufficient to evaluate stent apposition to the vessel wall. Statistical agreement on the scoring of stent visualization in all cases was strong (ICC=0.67). In 15 cases, CBCT identified important findings that could not be well delineated on conventional angiography or multidetector CT. These included: the relationship between a stent, a coil mass and important vessels originating in close proximity to an aneurysm, stent thrombosis, neointimal hyperplasia, stent malapposition and calcified atheroma underlying a stent. Conclusion CBCT is a reliable technique that provides good quality visualization of intracranial stents and their host vessels, enabling neuroradiologists to identify important findings that are not seen using standard methods. [ABSTRACT FROM PUBLISHER]

Purpose To describe our early experience with the balloon expandable Pharos Vitesse stent for symptomatic, high grade intracranial stenosis. Materials and methods Our center has enrolled five patients to date in the VISSIT (Vitesse Intracranial Stent Study for Ischemic Therapy) Trial. This prospective, multicenter, randomized trial is designed to compare best medical therapy alone to best medical therapy plus stenting for symptomatic, high grade intracranial stenosis. In conformance with the study design, patients were treated for 70–80% stenosis (inclusion criterion 70–99%) of the intracranial internal carotid, middle cerebral or intradural vertebral arteries. The patients ranged from 49 to 76 years of age (mean 63). There were four men and one woman. All target lesions and vessels were of appropriate size for treatment using the Pharos Vitesse stent. All patients underwent neurological assessment, including evaluation of the modified Rankin Scale (mRS) and CT studies prior to diagnostic digital subtraction angiography (DSA). Four patients also underwent CT perfusion (CTP). After diagnostic DSA, three patients were randomized to the stenting arm of the trial. One patient who was randomized to the medical therapy arm failed medical therapy and underwent stenting after recurrent ischemic stroke in the territory of the stenotic vessel. After stenting, mRS and CTP were performed in all patients prior to discharge. Results Stenting was technically successful in all cases. In three cases, there was no residual stenosis. In one case, heavily calcified, concentric atherosclerotic plaque resulted in residual stenosis of 30%. There were no procedural complications. One patient recovered from anesthesia with neurologic deficits localizable to the treated territory. These resolved completely and spontaneously within 24 h. No other periprocedural neurological adverse events were encountered. Two of three patients undergoing stenting had abnormal CTP findings in the territory distal to the stenotic lesion. In one, MTT was prolonged (>1.5× the contralateral side) in a large portion of the right middle cerebral artery (MCA) territory (90.8 cm tissue volume). In another, MTT was prolonged in the right MCA/posterior communicating artery watershed territory (5.3 cm tissue volume). All patients had normal CTP examinations at discharge. The 30 day mRS (median 1, range 0–6) were either stable or improved, compared with the mRS at presentation, in 3/4 patients. The fourth patient died >30 days after randomization due to complications of a previously unknown metastatic prostate cancer. The patient that was randomized to medical therapy awaits 30 day assessment. One patient returned 5 months after stenting with symptoms of transient ischemic attack in the treated territory. Although no residual stenosis was present initially, a flow restricting restenosis was identified on DSA. This was treated successfully using balloon angioplasty. Conclusion In our early experience, treatment of symptomatic, high grade intracranial stenosis with the Pharos Vitesse stent is a safe procedure that has resulted in no permanent procedure related complications. Following stenting, CTP showed completely restored blood flow to the pre-existing hypoperfused territories. The 30 day mRS score was stable or improved after stenting in 3/4 patients. [ABSTRACT FROM PUBLISHER]

Intra-hepatic cholestasis at pregnancy (ICP) is associated with prematurity, fetal distress, and intrauterine death. Homozygous mutations in the ATP8B 1 gene cause cholestasis with a normal serum gamma-glutamyl transpeptidase, and have been reported in two forms of cholestasis; progressive familial intrahepatic cholestasis type 1 and benign recurrent intrahepatic cholestasis. The role of ATPBB1 in the aetiology of ICP is not known. Authors aimed to establish whether mutations in ATP8B1 are associated with ICP. This is the first demonstration of ATP8B1 mutations in ICP, and the variants reported cause a new phenotype for mutations in this gene.

Purpose: Liver biopsy remains the gold standard for characterising and staging diffuse liver disease. This invasive test is associated with significant morbidity and, rarely, mortality. Our aim was to investigate whether a non-invasive technique, in vivo [sup 31]P-(MRS) could grade the severity of diffuse liver disease in patients whose liver disease was attributable to hepatitis C (HCV) infection only. Materials and Methods: Twelve controls and 47 patients with biopsy-proven HCV infection were studied prospectively. Based on their histological fibrosis (F) and necroinflammatory (NI) scores, patients were divided into mild hepatitis, n = 17 (F 2/6, NI 3/18); moderate/severe hepatitis, n = 19 (F 3/6, NI 4/18); and cirrhosis, n = 11 (F = 6). Hepatic [sup 31]P MR spectra were obtained using a 1.5 Tesla spectroscopy system (TR: 10 000; TE: 2). Results: There was a monotonic increase in the mean ± 1 s.e. phosphomonoester (PME) to phosphodiester (PDE) ratios for the control, mild hepatitis, moderate hepatitis and cirrhosis groups: 0.16 ± 0.01, 0.19 ± 0.07, 0.25 ± 0.02, 0.38 ± 0.04, respectively (ANOVA p < 0.001). No other significant spectral changes were observed. Conclusion: [sup 31]P MRS cannot diagnose HCV infection, but in patients with proven infection, this test can characterise the severity of liver disease. We have shown that the ratio of PME to PDE resonance in [sup 31]P MRS is able to separate mild from moderate hepatitis and these two groups from cirrhosis. The ability to differentiate these populations of patients has therapeutic implications and [sup 31]P MRS, in some situations, would not only complement a liver biopsy but could replace. [ABSTRACT FROM AUTHOR]

Introduction: The hepatic stellate (HSC) is known to synthesise the majority of excess matrix that characterises liver fibrosis and cirrhosis. Activated HSC also express matrix degrading metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). Whereas during spontaneous recovery from experimental liver fibrosis, there is a fall in the expression of the MMP inhibitor TIMP-1 and an increase in hepatic collagenolytic activity accompanied by HSC apoptosis; in advanced cirrhosis, TIMP-1 expression is maintained, and HSC persist. We have previously demonstrated that TIMP-1 can inhibit apoptosis of HSC by mechanisms involving MMP inhibition. We have studied the role of N-cadherin because it is known to be up regulated during HSC activation and may have a role in determining HSC survival and apoptosis. Aims: To determine the effect of blockade of N-cadherin binding on HSC; observe the fate of N-cadherin during HSC apoptosis; determine which MMP is involved and its direct effect on HSC. Results: By Western blot both rat and human HSC express 135kDa N-cadherin. Blockade of N-cadherin promoted apoptosis of HSC. During apoptosis of HSC there is cleavage of N-cadherin into fragments of 20-100kDa in size, which is protected by TIMP-1 and a selective inhibitor of MMP-2, but not inhibitors of MMP-1 or MMP-3 or a non functional mutant T2G TIMP-1. Active MMP-2 directly cleaves N-cadherin in vitro. Active MMP-2 also promotes apoptosis of HSC. Conclusions: These data suggest that the balance of MMP-2 and TIMP-1 determine HSC survival in hepatic fibrosis via stabilising N-cadherin. [ABSTRACT FROM AUTHOR]