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Biomedical subjects

S D Taylor-Robinson

Publications and source records attributed to S D Taylor-Robinson.

At least 19 recordsLinked to original sources
PubMed2005

In vivo imaging of cerebral "peripheral benzodiazepine binding sites" in patients with hepatic encephalopathy.

BACKGROUND AND AIMS: One proposed mechanism whereby hepatic encephalopathy (HE) leads to loss of brain function is dysregulated synthesis of neurosteroids. Mitochondrial synthesis of neurosteroids is regulated by "peripheral benzodiazepine binding sites" (PBBS). Expressed in the brain by activated glial cells, PBBS can be measured in vivo by the specific ligand [11C](R)-PK11195 and positron emission tomography (PET). Recently, it has been suggested that PBBS expressing glial cells may play a role in the general inflammatory responses seen in HE. Therefore, we measured PBBS in vivo in the brains of patients with minimal HE using [11C](R)-PK11195 PET. METHODS: Five patients with minimal HE and biopsy proven cirrhosis of differing aetiology were assessed with a neuropsychometric battery. Regional expression of PBBS in the brain was detected by [11C](R)-PK11195 PET. RESULTS: All patients showed brain regions with increased [11C](R)-PK11195 binding. Significant increases in glial [11C](R)-PK11195 binding were found bilaterally in the pallidum, right putamen, and right dorsolateral prefrontal region. The patient with the most severe cognitive impairment had the highest increases in regional [11C](R)-PK11195 binding. CONCLUSION: HE is associated with increased cerebral binding of [11C](R)-PK11195 in vivo, reflecting increased expression of PBBS by glial cells. This supports earlier experimental evidence in rodent models of liver failure, suggesting that an altered glial cell state, as evidenced by the increase in cerebral PBBS, might be causally related to impaired brain functioning in HE.

Aged↗
PubMed2005

Hepatic vein transit times using a microbubble agent can predict disease severity non-invasively in patients with hepatitis C.

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 < or =2/6, NI < or =3/18), moderate/severe hepatitis (3 < or =F <6 or NI > or =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. HVTTs 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 HVTT 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.

Adult↗
PubMed2005

Hepatic triglyceride content and its relation to body adiposity: a magnetic resonance imaging and proton magnetic resonance spectroscopy study.

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 (IQR 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 BMI <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 IMCL 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.

Abdomen↗
PubMed2005

ATP8B1 mutations in British cases with intrahepatic cholestasis of pregnancy.

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) affects approximately 0.7% of pregnancies in the UK and is associated with prematurity, fetal distress, and intrauterine death. Homozygous mutations in the ATP8B1 gene cause cholestasis with a normal serum gamma-glutamyl transpeptidase (gamma-GT), and have been reported in two forms of cholestasis: progressive familial intrahepatic cholestasis type 1 (PFIC1) and benign recurrent intrahepatic cholestasis (BRIC). AIMS: To establish whether mutations in ATP8B1 are associated with ICP in British cases PATIENTS: Sixteen well phenotyped women with ICP without raised gamma-GT were selected for sequence analysis. Subsequently, 182 patients and 120 controls were examined for the presence of the variants detected. METHODS: All coding exons were sequenced in 16 cases. Eight ICP cases, including two women carrying a mutation, were investigated using in vivo hepatic (31)P magnetic resonance spectroscopy (MRS) RESULTS: Two heterozygous ATP8B1 transitions (208G>A and 2599C>T) that resulted in amino acid substitutions were identified; 208G>A was identified in three cases. MRS revealed an increased phosphodiester signal (Mann-Whitney U test, p = 0.03) and a decreased phosphomonoester/phosphodiester ratio (p = 0.04) in ICP cases compared with controls. CONCLUSIONS: We were able to demonstrate ATP8B1 mutations in ICP. MRS studies suggest that susceptibility to ICP is associated with a relative rise in biliary phospholipid. These data also suggest that MRS may be used for non-invasive assessment of the liver and biliary constituents in cholestasis.

Adenosine Triphosphatases↗
PubMed2004

Fatigue and primary biliary cirrhosis: association of globus pallidus magnetisation transfer ratio measurements with fatigue severity and blood manganese levels.

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.

Adult↗
PubMed2003

Changes in brain intracellular pH and membrane phospholipids on oxygen therapy in hypoxic patients with chronic obstructive pulmonary disease.

Chronic hypoxia due to chronic obstructive pulmonary disease (COPD) constitutes a stress to cerebral metabolic homeostasis. Previous studies using phosphorus-31 magnetic resonance spectroscopy (31P MRS) have suggested that the brains of such patients utilize anaerobic glycolysis, which in neonatal, animal, and in vitro studies is associated with a protective intracellular alkalosis. To identify such a compensatory intracellular alkalosis in hypoxic COPD patients, in vivo cerebral 31P MRS was performed in eight patients and eight controls. The mean intracellular pH (pHi) in patients with COPD was similar to that of age-matched controls, but decreased in the patients with COPD by a mean pHi of 0.02 (p = 0.04), following supplemental oxygen. There was no change in cerebral pHi in normal subjects following oxygen administration. The broadband component of the MR spectrum increased in all the patients with COPD (p = 0.01), suggesting altered phospholipid membrane fluidity in the brain associated with the change in pHi following oxygen administration. The change in the broadband resonance was strongly correlated with the change in pHi (r = -0.68, p = 0.014). This study suggests that patients with COPD exhibit a compensatory change in pHi and abnormalities in cerebral membrane phospholipid conformation in the face of chronic hypoxia.

Adult↗
PubMed2003

Cerebral dysfunction in chronic hepatitis C infection.

A number of studies have reported an association between chronic hepatitis C (HCV) infection and significant impairments in health-related quality of life (QOL), which are independent of the severity of liver disease. There are numerous reports documenting the prevalence of symptoms such as fatigue and depression in chronic HCV infection, which may in part account for the reductions in quality of life. Although there are a large number of potential explanations for these symptoms, including depression and anxiety associated with the diagnosis of HCV infection or substance abuse, there has been recent interest in the possibility of a biological effect of HCV infection on cerebral function. There is emerging evidence of mild, but significant neurocognitive impairment in HCV infection, which cannot be attributed to substance abuse, coexistent depression or hepatic encephalopathy. In vivo magnetic resonance spectroscopy and neurophysiological studies have suggested that a biological mechanism may underlie these cognitive findings. The recent detection of HCV genetic sequences in post mortem brain tissue raises the intriguing possibility that HCV infection of the central nervous system may be related to the reported neuropsychological symptoms and cognitive impairment.

Brain Diseases↗
PubMed2003

MR-guided laser thermal ablation of primary and secondary liver tumours.

AIM: To test the hypothesis that magnetic resonance (MR)-guided hepatic tumour ablation is (i) safe and feasible, (ii) is associated with favourable patient survival, and (iii) decreases viable tumour. MATERIALS AND METHODS: One hundred and twenty-five MR-guided laser thermal ablations (LTA) were performed on 35 patients with hepatocellular carcinoma (HCC, n=19), hepatic metastases (n=11, mainly colorectal) and carcinoid liver tumours (n=5). RESULTS: Mean overall survival was 14.8 months (HCCs 14.6 months, metastases 15.2 months). Near real-time T1-weighted colourized thermal maps correlated moderately with follow-up gadolinium-enhanced MR imaging in predicting ablated tumour area (Pearson correlation coefficient=0.5). There was a significant difference in percentage enhancing pre- and post-LTA (Wilcoxon signed ranks test=0.0001). An average of 50.7% of tumour was ablated by each treatment. In patients with multiple liver tumours ablated tumours grew significantly less than untreated tumours (108%compared with 196% growth, follow-up period 5.8 months, WSRTp=0.07). CONCLUSION: MR- guided LTA of primary and secondary liver tumours is safe, feasible, and significantly decreased amount of enhancing or viable tumour. MR-guided LTA produces a better survival in patients with HCC than would be expected in untreated patients, and has a mean survival in patients with metastases at least equal to the longest median survival in untreated patients.

Aged↗
PubMed2003

DNA adducts, detected by 32P postlabelling, in human cholangiocarcinoma.

BACKGROUND: Reported mortality from intrahepatic cholangiocarcinoma (CCa) has risen steeply in the UK and other industrialised countries over the past 30 years, the cause of which has not been explained. DNA adduct formation is promutagenic and demonstrates exposure to a DNA damaging agent. It is a key step in chemically induced carcinogenesis. We hypothesise that the increase in CCa mortality is caused by a rise in a genotoxic environmental agent(s), causing cholangiocyte DNA damage. AIMS: To investigate and compare tumour and tumour adjacent CCa tissue, and non-cancer control bile duct tissue, for DNA adducts as a biomarker of genotoxin exposure. METHODS: DNA from 32 intrahepatic CCa patients (and in 28 cases DNA from adjacent non-tumour tissue) and from biliary ducts of seven non-cancer patients were investigated for the presence of DNA adducts using the nuclease P1 method of (32)P postlabelling. DNA adduct levels (number of adducts/10(8) nucleotides) were quantified. RESULTS: There was no significant difference in relative adduct labellings (RALs) between tumour adjacent DNA (median 8.6, range 1.2-51.6) and CCa DNA (7.2, 1.8-48.4). However, RALs were significantly higher in DNA from cancer patients (tumour adjacent and CCa DNA) compared with non-cancer patient DNA (2.9, 0.6-11.5; p=0.032, two tailed Mann-Whitney U test). Different adduct patterns were also seen in CCa compared with non-cancer patients. CONCLUSION: Quantitative and qualitative differences in adducts between cancer and non-cancer patients support the hypothesis that genotoxins may play a role in the development of intrahepatic CCa.

Adult↗
PubMed2003

Liver microbubble transit time compared with histology and Child-Pugh score in diffuse liver disease: a cross sectional study.

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.

Adult↗
PubMed2002

Ablative therapy for liver tumours.

Established ablative therapies for the treatment of primary and secondary liver tumours, including percutaneous ethanol injection, cryotherapy, and radiofrequency ablation, are discussed. Newer techniques such as magnetic resonance imaging guided laser interstitial thermal therapy of liver tumours has produced a median survival rate of 40.8 months after treatment. The merits of this newly emerging technique are discussed, together with future developments, such as focused ultrasound therapy, which holds the promise of non-invasive thermoablation treatment on an outpatient basis.

Catheter Ablation↗
PubMed2002

Operation Lifeline Sudan.

The provision of aid in war zones can be fraught with political difficulties and may itself foster inequalities, as it is rare to be allowed access to civilians on both sides of a conflict. Over the past decade, a United Nations (UN) brokered agreement has allowed Operation Lifeline Sudan (OLS), a UN "umbrella" organisation, to provide the diplomatic cover and operational support to allow long term humanitarian and emergency food aid to both the government and the rebel sides in the long-running south Sudanese civil war. Over the years, the destruction of infrastructure in the country has meant that the provision of basic health care has been seriously hampered. Operation Lifeline Sudan has coordinated the work of most of the non-governmental organisations (NGOs), working in this part of Africa. Each NGO has had responsibility for a particular area of the country and has worked closely with the local Sudanese authorities on either side of the conflict, conforming to strict codes of conduct or "ground rules", based on neutrality. Operation Lifeline Sudan has provided an air-bridge for emergency relief supplies in regions where road access is impossible, either because of landmines, or simply because the roads do not exist. The war continues, however, and the underlying causes of war-economic exploitation, marginalisation of communities, lack of political representation, and systematic violence and abuse remain unsolved. The warring factions have brought some OLS operations in south Sudan to a standstill recently, for certain political reasons that could have compromised the neutrality of the OLS-coordinated humanitarian aid schemes. It would appear that the only resolution to the country's problems are external political pressure to get the respective combatants to negotiate and, less probably, an undertaking by countries of the developed world not to continue to supply arms. Nevertheless, OLS may serve as a model for how medical aid can be delivered in an even-handed way to the populations of countries where there is civil war, irrespective of where they may live.

Delivery of Health Care↗
PubMed2002

Hepatocellular adenoma: diagnostic difficulties and novel imaging techniques.

We report the case of a 30-year-old eastern European female who presented with right upper quadrant pain. Clinical examination was unremarkable and liver function tests were normal. CT identified a 5 cm lesion in segment V of the liver, which was of homogeneous low density with no calcification or significant enhancement. MRI showed the lesion to be hypointense to liver on T(1) weighted sequences and isointense on T(2) weighted sequences. Rapid arterial enhancement with gadolinium-DTPA faded without leaving a definite central scar. Ultrasound showed the lesion to be echogenic with minimal vascularity. Administration of a liver-specific microbubble contrast agent showed low uptake relative to the surrounding liver. Phosphorus-31 MR spectroscopy, localized to the lesion itself, revealed a markedly increased phosphomonoester resonance with a decreased phosphodiester resonance, compatible with increased cell turnover. Biopsy confirmed the lesion to be a hepatocellular adenoma. The diagnosis of a hepatic adenoma is difficult with tissue diagnosis the gold standard, but it may be suggested by a combination of imaging modalities. We have described two new imaging techniques not previously described in characterization of hepatic adenomata, namely ultrasound with contrast agent and MR spectroscopy.

Adenoma↗