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Biomedical subjects

M Jackson

Publications and source records attributed to M Jackson.

At least 19 recordsLinked to original sources
PubMed2006

Course and outcome of acute limbic encephalitis with negative voltage-gated potassium channel antibodies.

BACKGROUND: Limbic encephalitis is a potentially treatable immunological condition. The presence of voltage-gated potassium channel antibodies (VGKC-Ab) in the cerebrospinal fluid (CSF) and serum of patients with the condition is a marker of the disease associated with a non-paraneoplastic form and good response to treatment. Recent work has highlighted absent serum VGKC-Ab and distinct immunology in patients with the paraneoplastic form of limbic encephalitis. METHODS: The cases of four patients with the typical clinical presentation, neuropsychological features and brain imaging of acute limbic encephalitis, in the absence of any evidence for associated cancer during a follow-up of at least 18 months are described here. RESULTS: All patients had negative testing for VGKC-Ab measured during their acute presentation. All patients made some recovery, although they were left with marked cognitive deficits and persistent seizures. CONCLUSION: These cases demonstrate that the absence of VGKC-Ab in limbic encephalitis does not necessarily imply a paraneoplastic form. Further work is required to establish the immunological basis for the disorder in these patients, and the optimal treatment regimen.

Acute Disease↗
PubMed2006

Curvature and tortuosity of the superficial femoral artery: a possible risk factor for peripheral arterial disease.

Atherosclerosis in the superficial femoral artery (SFA) resulting in peripheral arterial disease is more common in men than women and shows a predilection for the region of the adductor canal. Blood flow patterns are related to development of atherosclerosis, and we investigated if curvature and tortuosity of the femoral artery differed between young men and women and if differences resulted in adverse flow patterns. Magnetic resonance imaging (MRI) and computational fluid dynamics (CFD) were combined in 18 young adult volunteers (9 men) to assess the relationship of flow features to likely sites of future atherosclerosis formation. Subjects underwent MRI of the right SFA, three-dimensional vascular geometry was reconstructed, and measures of tortuosity and curvature were calculated. Tortuosity and curvature were significantly greater for men than women, and this was related to increased body surface area, body mass index, or weight in men. In both sexes, "tortuosity" increased from the midthigh to the popliteal fossa. The greatest curvature was found within the distal quarter of the SFA. CFD modeling was undertaken on MRI-based reconstructions of the SFA. Wall shear stresses (WSS) were extracted from the computations. WSS showed greater spatial variation in the men than in the women, and the men exhibited lower mean WSS. These data indicate that sex differences related to body size and anatomical course of the femoral artery may contribute to the enhanced risk of focal atherosclerosis in the adductor canal.

Adult↗
PubMed2006

Comparison of methods of assessment of renal function in cystic fibrosis (CF) patients.

Renal failure is increasingly being recognised in CF patients, usually as a consequence of long-term nephrotoxic therapy. There is a need for a simple method of assessment of renal function in this patient group. We compared measured creatinine clearance from validated timed urine collections (the generally accepted practical test of glomerular filtration) with 10 formulae used to estimate creatinine clearance in a group of 74 CF adult patients and 29 matched normal controls. Compared to direct measurement, formulae gave a range of values (95% CI for mean bias -13 to +27.9 ml/min). Even those with the best correlation (r=0.7) gave wide error ranges (limits of agreement: -42.3 to 45.9 ml/min). The most commonly used formulae (Cockroft-Gault [CGF] and abbreviated Modification of Diet in Renal Disease [aMDRD]) were not superior to most other formulae tested. Both CGF and aMDRD-derived estimates compared less favourably in CF patients than controls (mean bias: 9.7 vs 3.4 ml/min (p<0.05) and 4.9 vs 1.4 (p<0.05) respectively; 78% vs 95% (p<0.01) and 77% vs 97% (p<0.01) of estimates within 33% of measurement respectively). In particular, both CGF and aMDRD grossly overestimated renal function (mean bias 18.3 and 15.8 ml/min respectively, p<0.001) in CF patients with reduced creatinine clearance (<80 ml/min). CGF, aMDRD and other formulae cannot be used to reliably assess renal function in CF patients, since they will fail to detect those with renal impairment. Some form of carefully supervised direct measurement is still required.

Adolescent↗
PubMed2006

Early, sustained efficacy of adeno-associated virus vector-mediated gene therapy in glycogen storage disease type Ia.

The deficiency of glucose-6-phosphatase (G6Pase) underlies life-threatening hypoglycemia and growth retardation in glycogen storage disease type Ia (GSD-Ia). An adeno-associated virus (AAV) vector encoding G6Pase was pseudotyped as AAV8 and administered to 2-week-old GSD-Ia mice (n = 9). Median survival was prolonged to 7 months following vector administration, in contrast to untreated GSD-Ia mice that survived for only 2 weeks. Although GSD-Ia mice were initially growth-retarded, treated mice increased fourfold in weight to normal size. Blood glucose was partially corrected by 2 weeks following treatment, whereas blood cholesterol normalized. Glucose-6-phosphatase activity was partially corrected to 25% of the normal level at 7 months of age in treated mice, and blood glucose during fasting remained lower in treated, affected mice than in normal mice. Glycogen storage was partially corrected in the liver by 2 weeks following treatment, but reaccumulated to pre-treatment levels by 7 months old (m.o.). Vector genome DNA decreased between 3 days and 3 weeks in the liver following vector administration, mainly through the loss of single-stranded genomes; however, double-stranded vector genomes were more stable. Although CD8+ lymphocytic infiltrates were present in the liver, partial biochemical correction was sustained at 7 m.o. The development of efficacious AAV vector-mediated gene therapy could significantly reduce the impact of long-term complications in GSD-Ia, including hypoglycemia, hyperlipidemia and growth failure.

Animals↗
PubMed2006

Autophagic vacuolar myopathy in twin girls.

Hereditary autophagic vacuolar myopathy (AVM) may occur in several diseases including the rimmed vacuolar myopathies, acid maltase deficiency, Danon disease, infantile autophagic vacuolar myopathy and X-linked myopathy with excessive autophagy (XMEA). In the latter three conditions the vacuoles are lined by membranes with sarcolemmal features. We present two unusual cases of autophagic vacuolar myopathy in twin girls born at term with no family history of neurological disease. After initial normal developmental milestones they developed progressive leg weakness and wasting with contractures from the age of 12 years. Investigations showed raised CK, normal female karyotype, normal acid maltase activity, normal nerve conduction and myopathic EMG features. Frozen sections of skeletal muscle were stained using routine tinctorial and histochemical methods. Immunohistochemical staining for spectrin, merosin, dystrophin, complement membrane attack complex and sarcoglycans was performed and ultrastructural examination undertaken. Direct sequence analysis of the lamp-2 gene using genomic DNA extracted from lymphocytes was performed. Histological analysis of the muscle biopsies demonstrated myofibres with vacuoles lacking glycogen and lipid many of which were delineated using immunohistochemistry for merosin, dystrophin and sarcoglycans. Ultrastructural examination showed duplication of the myofibre basal lamina with associated autophagic material. Vacuoles within myofibres were either membrane bound containing autophagic material or lined by plasma membrane and basal lamina. Intermyofibrillar glycogen was increased. Sequence analysis of the coding region and intron/exon boundaries of the lamp-2 gene was normal. This is the first report of female cases of AVM with sarcolemmal features. We suggest that these patients may represent manifesting carriers of XMEA, or alternatively, a new form of disease with a similar phenotype having autosomal recessive inheritance.

Adolescent↗
PubMed2006

Mental well-being of doctors and nurses in two hospitals in Kingston, Jamaica.

Hospital work involves some of the most stressful situations found in any workplace. Furthermore, hospital workers may be affected by non-work-related stress such as family responsibilities and financial difficulties, leading to impaired mental well-being and suboptimal performance. The aim of this study was to assess the level of general mental well-being among doctors and nurses from two hospitals in Kingston, Jamaica. A total of 212 doctors and nurses at the Kingston Public Hospital and the University Hospital of the West Indies were studied yielding a participation rate of 83.1%. A self-administered questionnaire was used to gather social and biomedical data and the General Health Questionnaire 30 (GHQ 30) used to determine general mental well-being. Probable caseness was defined as a GHQ 30 score > 5. Focus group discussions were also held with staff at both hospitals. A total of 27.4% of the study population met the GHQ-30 criteria (caseness) defining them as probable cases of mental distress. Cases and non-cases were not different in age, gender or hospital of employment. However, caseness was associated with years of professional experience, work-related and non-work-related stress, serious financial difficulties and fears of coming to work. Significant predictors of increased risk of caseness were fear of coming to work (OR 3.06; CI 1.40, 6.70); professional experience in excess of five-years and high non-work-related stress. High work-related stress was associated with reduced risk of being classified a case, suggesting that work may have been therapeutic. Focus group discussions suggested that non-work stress was related to financial difficulties, commuting and child care, especially among nurses. Intervention to improve general mental well-being should be targeted at new employees and should address child care, commuting and financial management.

Adaptation, Psychological↗
PubMed2005

Intrafractional motion during proton beam scanning.

Patient and internal organ motion during treatment with a scanned proton beam can introduce unplanned heterogeneities in the dose distribution throughout the irradiated volume. With static beam techniques, a margin around the target volume is added to compensate for patient and organ motion. This margin may not provide the solution with dynamic beam scanning. Intrafractional motion parallel and perpendicular to the beam axis is studied using two different scanning methods on a cubic water phantom. The direction of motion relative to the beam scanning direction as well as the method of scanning the proton beam across the target has a significant effect on the resulting dose distribution within the target volume. In the extreme cases studied here up to 100% of the target receives a dose outside the recommended limits, with a minimum dose as low as 34% of the prescribed dose.

Algorithms↗
PubMed2005

Multivariate prediction of major adverse cardiac events after 9914 percutaneous coronary interventions in the north west of England.

OBJECTIVE: To develop a multivariate prediction model for major adverse cardiac events (MACE) after percutaneous coronary interventions (PCIs) by using the North West Quality Improvement Programme in Cardiac Interventions (NWQIP) PCI Registry. SETTING: All NHS centres undertaking adult PCIs in north west England. METHODS: Retrospective analysis of prospectively collected data on 9914 consecutive patients undergoing adult PCI between 1 August 2001 and 31 December 2003. A multivariate logistic regression analysis was undertaken, with the forward stepwise technique, to identify independent risk factors for MACE. The area under the receiver operating characteristic (ROC) curve and the Hosmer-Lemeshow goodness of fit statistic were calculated to assess the performance and calibration of the model, respectively. The statistical model was internally validated by using the technique of bootstrap resampling. MAIN OUTCOME MEASURES: MACE, which were in-hospital mortality, Q wave myocardial infarction, emergency coronary artery bypass graft surgery, and cerebrovascular accidents. RESULTS: Independent variables identified with an increased risk of developing MACE were advanced age, female sex, cerebrovascular disease, cardiogenic shock, priority, and treatment of the left main stem or graft lesions during PCI. The ROC curve for the predicted probability of MACE was 0.76, indicating a good discrimination power. The prediction equation was well calibrated, predicting well at all levels of risk. Bootstrapping showed that estimates were stable. CONCLUSIONS: A contemporaneous multivariate prediction model for MACE after PCI was developed. The NWQIP tool allows calculation of the risk of MACE permitting meaningful risk adjusted comparisons of performance between hospitals and operators.

Adult↗
PubMed2005

Monitoring the development of hepatocellular carcinoma in woodchucks using 31P-MRS.

The woodchuck is one of the only lab animal models of chronic viral hepatitis infection and the development of hepatocellular carcinoma. Using this model, changes in tissue energetics in the liver due to the development of hepatocellular carcinoma can be monitored by repeated magnetic resonance imaging and localized phosphorus spectroscopy. Age- and sex-matched control (n=5) and chronically infected (n=5) adult woodchucks were imaged four times in a six-month period in a 7-T horizontal-bore magnet. Using a custom-built doubly tunable quadrature volume coil, sagittal and axial FLASH images (128 x 128, slice thickness = 5 mm, TR/TE=1000/4.1, 8 averages) were acquired to locate the largest portion of the liver with the least amount of signal contamination from surrounding abdominal muscle. Two-dimensional 31P chemical-shift imaging (2D-CSI) was acquired (16 x 16 data matrix, 24 x 24 x 2 cm3, 1024 data points, 16 averages) for all animals. The extent of liver injury was determined using serum gamma glutamyltransferase (GGT). The livers of infected woodchucks showed a significant increase (p=0.01) in phosphomonoesters (PME):beta-adenosine triphosphate (NTP). Chronically infected woodchucks had higher levels of serum GGT compared to uninfected woodchucks (p=0.002). An increase in the PME:beta-NTP ratio indicates cellular proliferation within the malignant tumor.

Animals↗
PubMed2005

In vitro response of tumour cells to non-uniform irradiation.

This study examines differences in tumour cellular response using clonogenic cell survival between uniform and non-uniform irradiation. Cells were irradiated with a 6 MV x-ray intensity-modulated beam, in a single large flask (i.e. intercellular communication is possible) or in three small flasks (i.e. intercellular communication is inhibited across the dose gradient). For non-small-cell lung cancer and melanoma cell lines, the dose response over the entire cell culture was significantly different between freely communicating cell cultures and those with inhibited communication across the dose non-uniformity. Communicating cells exhibited poorer survival in the low dose region of the field but improved survival in the high dose region. In general, the response to non-uniform irradiation appeared to 'average out' over the entire cell culture. This was not seen when intercellular communication was inhibited. The results add strength to the body of evidence regarding bystander effects and the inter-dependence of cellular response.

Carcinoma, Large Cell↗
PubMed2005

Proteasomal activity in brain differs between species and brain regions and changes with age.

Age-related increase in protein oxidation in brain coupled to an impairment of proteasomal activity may underline neuronal loss but differences in susceptibility between species and brain regions remain unexplained. We now investigate differences in proteasomal activity, measured as chymotrypsin-, trypsin- and peptidylglutamyl-like hydrolysing activities between brain regions in rats, mice and common marmosets. In aged rats and mice, proteasomal activity was decreased in the cortex, striatum, cerebellum, globus pallidus and substantia nigra overall when compared to young animals. However, in the aged brain only chymotrypsin-like activity was decreased in the cortex and the globus pallidus while only trypsin-like activity was reduced in the cerebellum. In contrast, in the striatum, both chymotrypsin-like and trypsin-like activities were reduced and in the substantia nigra, all the three catalytic activities of proteasome were significantly impaired. Chymotrypsin-like and trypsin-like activities were significantly higher in all the brain regions of marmosets compared to those of mice and rats. Peptidylglutamyl-like activity was only significantly higher in the cerebellum and striatum of marmoset compared to rodents. The data suggest that there is higher proteasome activity in common marmoset brain compared to rat and mouse and that the basal ganglia are more prone to an age-related decrease in proteasomal activity. This may explain the involvement of altered ubiquitin-proteasome system activity in Parkinson's disease and the relationship to ageing.

Aging↗
PubMed2005

Plasma insulin growth factor-1 and incident delirium in older people.

BACKGROUND: A variety of demographic and clinical variables are acknowledged as risk factors for delirium; a syndrome thought to be mediated by abnormalities in a wide range of neurotransmitters. However, little research has been conducted in this field and the role of neuro-immunological factors as a mechanism of medication has received very little attention. AIMS: To determine if low base line (on admission) IGF-1 levels (a protective cytokine released by brain cells in response to insult) is a risk factor for incident delirium in patients aged 75 and over admitted to an acute medical ward. METHOD: Base line demographic and clinical variables and serum IGF-1 levels were measured in a consecutive series of 100 non-delirious subjects on inpatient admission. Subjects were assessed daily regarding the development of delirium during the inpatient episode. RESULTS: Twelve patients developed incident delirium. IGF-1 (OR: 0.822, CI: 0.69, 0.97, p = 0.027), pre-admission cognitive deterioration (assessed by IQCODE) (OR; 3.26, CI: 1.18, 9.04, p = 0.023) and depression (GDS four item: cut-off score > or = 3) (OR; 8.99, CI 1.59,50.76, p = 0.013) were identified as risk factors for developing subsequent delirium. CONCLUSIONS: Despite the small size of this study our findings suggest that low, pre-morbid IGF-1 is a risk factor for subsequent delirium in this population, emphasizing the potential protective role of this anabolic cytokine and the need for replication of these findings.

APACHE↗
PubMed2005

Molecular defects in Sanfilippo syndrome type B (mucopolysaccharidosis IIIB).

Sanfilippo syndrome type B (mucopolysaccharidosis IIIB) is an autosomal recessive disease that is caused by the deficiency of the lysosomal enzyme alpha-N-acetylglucosaminidase (NAGLU). NAGLU is involved in the degradation of the glycosaminoglycan (GAG) heparan sulphate, and a deficiency results in the accumulation of partially degraded GAGs inside lysosomes. Early clinical symptoms include hyperactivity, aggressiveness and delayed development, followed by progressive mental deterioration, although there are a small number of late-onset attenuated cases. The gene for NAGLU has been fully characterized and we report the molecular analysis of 18 Sanfilippo B families. In total, 34 of the 36 mutant alleles were characterized in this study and 20 different mutations were identified including 8 novel changes (R38W, V77G, 407-410del4, 703delT, A246P, Y335C, 1487delT, E639X). The four novel missense mutations were transiently expressed in Chinese hamster ovary cells and all were shown to decrease the NAGLU activity markedly, although A246P did produce 12.7% residual enzyme activity.

Acetylglucosaminidase↗
PubMed2005

Automated classification of peripheral distal by-pass geometries reconstructed from medical data.

Abnormal haemodynamic conditions are implicated in the development of anastomotic myointimal hyperplasia (MIH). However, these conditions are difficult to determine in vivo, prompting research using ex vivo idealised models. To relate the understanding gained in idealised geometries to anatomically correct conditions we have investigated a reproducible approach to classify in vivo distal graft anastomoses and their inter-patient variability. In vivo distal anastomotic geometries were acquired by magnetic resonance (MR) angiography from 13 patients who had undergone infrageniculate autologous venous by-pass surgery. On average, the images were acquired 2 weeks post-operatively. Five patients also underwent repeat examinations 2 to 7 weeks later. For each geometry, the surface of the arterial lumen is represented by the zero level set of an implicit function constructed from radial basis functions that minimise curvature. The three-dimensional binary image created from the interpolated surface is processed using a skeletonisation algorithm to obtain the centreline of each branch in the geometry. This allows for the measurement of the branching angles between straight line approximations of the centrelines of each vessel, averaging them over a characteristic length of each anastomosis. The main finding in the application of the proposed classification methodology to this set of patients is that the spectrum of anastomoses can be reduced to a small subset of cases characterised by two angles: the angle between the graft and the plane of the host artery and the angle between the graft and the proximal branch of the artery.

Algorithms↗
PubMed2005

[Anatomy of the splint bones and their surrounding area particularly in consideration of fascial attachments].

This study concerns the vestigial metacarpal and metatarsal bones, so called splint bones. The soft tissues, which stabilize the splint bones were carefully examined. The palmar metacarpal/plantar metatarsal fascia, the metacarpal/metatarsal interosseous ligaments and the fibres, which exit distally from the splint bone, were examined in depth. Cadaveric distal limbs were collected from 5 slaughtered or euthanized horses. The legs were examined both, microscopically and macroscopically. The palmar metacarpal/plantar metatarsal fascia is a very stable structure, which connects the splint bone with its environment. The connection between splint and McIII/MtIII, established through the metacarpal/ metatarsal interosseous ligaments, showed impressive differences between specimens examined. Macroscopic examination of the soft tissue in the distal region showed a band structure, which originates from the distal end of the splint bone and extends in dorsal and distal direction towards the proximal sesamoid bone.

Animals↗
PubMed2005

Anatomy of pilon fractures of the distal tibia.

In a series of 126 consecutive pilon fractures, we have described anatomically explicable fragments. Fracture lines describing these fragments have revealed ten types of pilon fracture which belong to two families, sagittal and coronal. The type of fracture is dictated by the energy of injury, the direction of the force of injury and the age of the patient.

Adult↗