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Biomedical subjects

M O'Sullivan

Publications and source records attributed to M O'Sullivan.

At least 37 records · Page 2Linked to original sources
PubMed2002

Patterns of cerebral blood flow reduction in patients with ischemic leukoaraiosis.

BACKGROUND: Ischemic leukoaraiosis (ILA) refers to diffuse T2-weighted white matter hyperintensity in the context of a previous clinical lacunar stroke. Reduced cerebral blood flow (CBF) in white matter has been demonstrated, but it is not known whether hypoperfusion is confined to lesions or extends into normal-appearing white matter. Demonstrating changes in normal-appearing white matter would provide clues to the importance of hypoperfusion in pathogenesis and would be an obvious target for therapies aimed at restoring white matter blood flow. METHODS: Twenty-one patients with ILA, and 16 age-matched control subjects, underwent exogenous contrast-based quantitative perfusion MRI. CBF was determined both within and outside areas of T2-weighted hyperintensity in both periventricular white matter and the centrum semiovale. RESULTS: CBF of normal-appearing white matter was reduced in periventricular regions (for patients with ILA, 17.9 +/- 5.6 mL/100 g/min; for controls, 21.6 +/- 5.1 mL/100 g/min; p = 0.046). CBF in gray matter and normal-appearing white matter of the centrum semiovale did not differ significantly between groups. In normal-appearing white matter in patients, CBF was higher in the centrum semiovale than periventricular white matter, with a similar trend in control subjects. CONCLUSIONS: Hypoperfusion may be an early feature in the development of periventricular lesions in ILA and may play a direct pathogenic role. Serial studies are now needed to determine whether these changes herald the appearance of new lesions and represent "at risk" white matter, and to determine whether pharmacological agents can restore perfusion of normal-appearing white matter.

Aged↗
PubMed2002

Immunolocalization of semicarbazide-sensitive amine oxidase in human dental pulp and its activity towards serotonin.

The semicarbazide-sensitive amine oxidase (EC 1.4.3.6; SSAO) from crude homogenates of human dental pulp was shown to catalyse the oxidative deamination of 5-hydroxytryptamine (serotonin; 5-HT) with a K(m) of 318+/-52 microM. In this respect the human enzyme resembles that in pig dental pulp, but differs from SSAO in all other tissues studied, which are inactive towards 5-HT. A method is described for obtaining intact dental pulp in which the anatomical details are preserved. Extracted teeth are frozen in dry ice and later defrosted rapidly before being fractured in a mechanical vice, facilitating pulp removal. Immunohistochemistry showed SSAO in the odontoblast layer, nerve fibres and blood vessels. The presence of SSAO in nerves in dental pulp appears to be unique. Tryptophan hydroxylase, a key enzyme in 5-HT synthesis, was also demonstrated in nerves and the odontoblast layer of human dental pulp.

Amine Oxidase (Copper-Containing)↗
PubMed2002

Restricted matrilineal gene flow and regional differentiation among Atlantic salmon (Salmo salar L.) populations within the Bay of Fundy, eastern Canada.

Matrilineal phylogenetic divergence among Atlantic salmon stocks of the Bay of Fundy in south eastern Canada is investigated. Sequence variation in two regions of the mitochondrial ND1 gene, encompassing 710 base pairs, is described for 168 salmon from 11 rivers. Mean overall haplotype and nucleotide diversity (h and pi) observed are 0.5014 and 0.00095, respectively. Nested clade analysis (NCA) and molecular analysis of variance (AMOVA) both point to highly restricted gene flow among rivers and show the haplotype distribution to be geographically structured. Variation among predefined regions of the Bay (16%) is greater than among populations within these regions (14%) The main regional differentiation occurs between rivers of the geographically isolated inner Minas Basin and those elsewhere in the Bay. Differentiation most probably reflects the pattern and nature of the historical processes associated with post-glacial colonisation of the area by salmon following the last Pleistocene glacial maximum c. 180,00 yrs BP.

Animals↗
PubMed2002

TGF beta-1 downregulates DMP-1 and DSPP in odontoblasts.

Transforming growth factor beta-1 (TGF beta-1) is a multifunctional growth factor that is expressed in numerous cell types. It has been shown to induce secretion of dentin extracellular matrix components associated with primary dentinogenesis and to play a role in tertiary or reparative dentinogenesis. In this study, we investigated the potential transcriptional regulation by TGF beta-1 of two dentin matrix proteins: dentin matrix protein 1 (DMP-1), and dentin sialophosphoprotein (DSPP). In vitro promoter studies were performed using plasmid constructs containing mouse DMP-1 and DSPP promoter sequences fused to the luciferase reporter gene. Constructs were transiently transfected in the mouse odontoblast cell line M06-G3 and cultured in the presence or absence of TGF beta-1. The integrity of the TGF beta-1 signaling pathway was investigated in the M06-G3 cells by identifying known key effectors of TGF beta-1 signal transduction. Transient transfection studies demonstrate for the first time that TGF beta-1 downregulates both DMP-1 and DSPP genes. Our findings indicate that the TGF beta-1 type I receptor ALK5 is expressed by odontoblasts as well as the signal transduction proteins Smad2, Smad3, and Smad4. These results suggest that TGF beta-1 regulates two key dentin proteins involved in matrix mineralization most likely mediated through the type I ALK5 receptor and transduced by Smads 2, 3, and 4.

Activin Receptors, Type I↗
PubMed2002

Aneursymal bone cyst of the proximal phalanx of the thumb in a child.

Aneursymal Bone Cysts (ABCs) involving the hand are a rare occurrence. We report a case of an ABC of the proximal phalanx of the thumb in a boy which was treated successfully with curettage and autologous bone grafting. When the diagnosis of ABC of the small bones of the hand is entertained, prompt therapeutic intervention is indicated because of the potential for aggressive local behaviour. In the paediatric patient, simple surgery to preserve the growth plate is recommended.

Bone Cysts, Aneurysmal↗
PubMed2002

Carditis: all Helicobacter pylori or is there a role for gastro-oesophageal reflux?

BACKGROUND: Recent epidemiological studies have reported a threefold increase in the incidence of adenocarcinoma of the lower oesophagus and gastro-oesophageal junction (cardia). There are conflicting reports available implicating both gastro-oesophageal reflux disease and Helicobacter pylori infection in the aetiology of carditis and cardia intestinal metaplasia, despite strong evidence to show that these two conditions are, if anything, inversely related. We aimed to determine the prevalence of carditis and cardia intestinal metaplasia in dyspeptic subjects and also their association with H. pylori infection and gastro-oesophageal reflux disease. METHOD: Histological samples from the gastric cardia were obtained from dyspeptic subjects. H. pylori status was assessed based on histological, microbiological and rapid urease testing. Gastro-oesophageal disease was diagnosed on the basis of histological evidence and/or erosive oesophagitis. Patient demographics were recorded. Cardia intestinal metaplasia (CIM), when present, was subgrouped as complete or incomplete. RESULTS: Overall, 276 subjects were enrolled; 163 (59%) had carditis and 36 (13%) CIM. H. pylori infection and gastro-oesophageal reflux disease occurred in 64 (23%) and 150 (54%), respectively. H. pylori infection was strongly associated with carditis and CIM (P<0.001 and P<0.01). Older age and male gender were also associated with inflammation and intestinal metaplasia of the cardia. Gastro-oesophageal reflux was not associated with either entity. CONCLUSION: Carditis and CIM occur frequently. Both conditions are strongly associated with H. pylori infection, older age and male gender. There was no association with gastro-oesophageal reflux disease.

Adolescent↗
PubMed2001

Normal-appearing white matter in ischemic leukoaraiosis: a diffusion tensor MRI study.

Ischemic leukoaraiosis is a consistent concomitant of vascular dementia. Conventional MRI provides little information about underlying white matter tract disruption and correlates poorly with cognitive dysfunction. Diffusion tensor MRI may provide better markers of tract integrity. Changes in the normal-appearing white matter were demonstrated in 30 patients with ischemic leukoaraiosis compared with 17 age-matched control subjects. These changes correlated with executive dysfunction assessed by the Wisconsin Card Sorting Test.

Aged↗
PubMed2001

Evidence for cortical "disconnection" as a mechanism of age-related cognitive decline.

BACKGROUND: Normal aging is accompanied by a decline of cognitive abilities, and executive skills may be affected selectively, but the underlying mechanisms remain obscure and preventive strategies are lacking. It has been suggested that cortical "disconnection" due to the loss of white matter fibers may play an important role. But, to date, there has been no direct demonstration of structural disconnection in humans in vivo. METHODS: The authors used diffusion tensor MRI to look for evidence of ultrastructural changes in cerebral white matter in a group of 20 elderly volunteers with normal conventional MRI scans, and a group of 10 younger controls. The older group also underwent neuropsychological assessment. RESULTS: Diffusional anisotropy, a marker of white matter tract integrity, was reduced in the white matter of older subjects and fell linearly with increasing age in the older group. Mean diffusivity was higher in the older group and increased with age. These changes were maximal in anterior white matter. In the older group, anterior mean diffusivity correlated with executive function assessed by the Trail Making Test. CONCLUSIONS: These findings provide direct evidence that white matter tract disruption occurs in normal aging and would be consistent with the cortical disconnection hypothesis of age-related cognitive decline. Maximal changes in anterior white matter provide a plausible structural basis for selective loss of executive functions. In addition to providing new information about the biological basis of cognitive abilities, diffusion tensor MRI may be a sensitive tool for assessing interventions aimed at preventing cognitive decline.

Adult↗
PubMed2001

MRI hyperintensities of the temporal lobe and external capsule in patients with CADASIL.

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited, autosomal dominant condition caused by mutations of the Notch3 gene. Affected individuals have migraine, mood disturbance, and recurrent strokes, often progressing to subcortical dementia and premature death. MRI findings include focal lacunar infarcts and diffuse T2-weighted hyperintensity, or leukoaraiosis. However, such findings are seen much more commonly in patients with cardiovascular risk factors, particularly hypertension, where they are believed to represent cerebral small vessel disease. No previous study has sought to identify specific radiologic markers of CADASIL. METHODS: MRI scans from 20 consecutive patients with CADASIL and 20 patients with sporadic leukoaraiosis due to presumed small-vessel disease were compared using the previously validated semiquantitative MRI rating scale devised by Scheltens et al. Analysis was blinded to clinical category. RESULTS: Scores for hyperintensities of the temporal white matter and external capsule-insula region were significantly higher in patients with CADASIL. Hyperintensity confined to the pole of the temporal lobe was a characteristic finding in CADASIL, occurring in 19 patients with CADASIL but no patients with ischemic leukoaraiosis. Involvement of the external capsule, though less specific, was seen early in the disease course. In a few patients with CADASIL, involvement of the corpus callosum was observed. CONCLUSIONS: Temporal pole hyperintensity is a radiologic marker of CADASIL. Involvement of the external capsule and corpus callosum are also characteristic findings that may help to distinguish the disease.

Adult↗
PubMed2001

Outcome of compartment syndrome following intramedullary nailing of tibial diaphyseal fractures.

Seventeen cases of compartment syndrome were treated in a group of 626 consecutive patients with tibial diaphyseal fractures. Clinical and radiological follow-up was performed at an average of 24 months (range 8-54 months). Functional outcome was assessed using Edward's classification. All patients who developed compartment syndrome had fracture stabilisation with a reamed intramedullary nail using skeletal traction. The average interval between the nailing procedure and fasciotomy was 11 h. Results were good in 10 cases, fair in four cases and poor in the remaining three cases. Patients who had decompression within 12 h had a good functional outcome. Patients with poor results were all treated at an interval greater than 24 h.

Adult↗
PubMed2001

Antegrade locked intramedullary nailing in humeral shaft fractures.

Thirty-three humeral nailings were carried out using the Russell-Taylor nail. Twenty-two acute fractures and one non-union united, gave an overall union rate of 70%. Eighteen patients (56%) experienced pain in the shoulder or at the fracture site. Thirteen patients (41%) had poor shoulder function. Only 17 (51%) of the patients were satisfied with the outcome. Fourteen patients (42%) needed further surgery. We conclude that antegrade intamedullary nailing of humeral shaft fractures leads to a substantial risk of non-union and impairment of shoulder function. There was no significant correlation between fracture comminution and fracture healing in our study.

Adult↗
PubMed2001

Mechanisms of angioplasty and stent restenosis: implications for design of rational therapy.

Restenosis after angioplasty or stenting remains the major limitation of both procedures. A vast array of drug therapies has been used to prevent restenosis, but they have proven to be predominantly unsuccessful. Recent trends in drug therapy have attempted to refine the molecular and biological targets of therapy, based on the assumption that a single biological process or molecule is critical to restenosis. In contrast, both stenting and brachytherapy, which are highly nonspecific, can successfully reduce restenosis after angioplasty or stenting, respectively. This review examines the biology of both angioplasty and stent stenosis, focussing on human studies. We also review the landmark human trials that have definitively proven successful therapies, such as stenting and brachytherapy. We suggest that the successful trials of stenting and brachytherapy and the failure of other treatments have highlighted the shortcomings of conventional animal models of arterial intervention, and gaps in our knowledge of human disease. In contrast to arguments advocating gene therapy, these studies suggest that the most likely successful drug therapy will have a wide therapeutic range, targeting as many of the components or biological processes contributing to restenosis as possible.

Angioplasty↗
PubMed2001

MRI based diffusion and perfusion predictive model to estimate stroke evolution.

In this study we present a novel automated strategy for predicting infarct evolution, based on MR diffusion and perfusion images acquired in the acute stage of stroke. The validity of this methodology was tested on novel patient data including data acquired from an independent stroke clinic. Regions-of-interest (ROIs) defining the initial diffusion lesion and tissue with abnormal hemodynamic function as defined by the mean transit time (MTT) abnormality were automatically extracted from DWI/PI maps. Quantitative measures of cerebral blood flow (CBF) and volume (CBV) along with ratio measures defined relative to the contralateral hemisphere (r(a)CBF and r(a)CBV) were calculated for the MTT ROIs. A parametric normal classifier algorithm incorporating these measures was used to predict infarct growth. The mean r(a)CBF and r(a)CBV values for eventually infarcted MTT tissue were 0.70 +/- 0.19 and 1.20 +/- 0.36. For recovered tissue the mean values were 0.99 +/- 0.25 and 1.87 +/- 0.71, respectively. There was a significant difference between these two regions for both measures (p < 0.003 and p < 0.001, respectively). Mean absolute measures of CBF (ml/100g/min) and CBV (ml/100g) for the total infarcted territory were 33.9 +/- 9.7 and 4.2 +/- 1.9. For recovered MTT tissue, the mean values were 41.5 +/- 7.2 and 5.3 +/- 1.2, respectively. A significant difference was also found for these regions (p < 0.009 and p < 0.036, respectively). The mean measures of sensitivity, specificity, positive and negative predictive values for modeling infarct evolution for the validation patient data were 0.72 +/- 0.05, 0.97 +/- 0.02, 0.68 +/- 0.07 and 0.97 +/- 0.02. We propose that this automated strategy may allow possible guided therapeutic intervention to stroke patients and evaluation of efficacy of novel stroke compounds in clinical drug trials.

Aged↗
PubMed2001

Microencapsulating properties of sodium caseinate.

Emulsions were prepared with 5% (w/v) solutions of sodium caseinate (Na Cas) and soy oil at oil/protein ratios of 0.25-3.0 by homogenization at 10--50 MPa. Emulsions were spray-dried to yield powders with 20--75% oil (w/w). Emulsion oil droplet size and interfacial protein load were determined. Microencapsulation efficiency (ME), redispersion properties, and structure of the powders were analyzed. The size of emulsion oil droplets decreased with increasing homogenization pressure but was not influenced by oil/protein ratio. Emulsion protein load values were highest at low oil/protein ratios. ME of the dried emulsions was not affected by homogenization pressure but decreased from 89.2 to 18.8% when the oil/protein ratio was increased from 0.25 to 3.0, respectively. Mean particle sizes of reconstituted dried emulsions were greater than those of the original emulsions, particularly at high oil/protein ratios (>1.0), suggesting destabilization of high-oil emulsions during the spray-drying process.

Caseins↗
PubMed2001

Effect of partial replacement of gum arabic with carbohydrates on its microencapsulation properties.

Gum arabic solutions (10% w/v) were emulsified with soy oil at oil/gum ratios of 0.25-5.0. At oil/gum ratios <1.0, it was established that gum arabic could be partially replaced with a nonsurfactant carbohydrate. To assess different carbohydrates as replacers for gum arabic, emulsions and spray-dried emulsions of soy oil and mixed solutions (10% w/v) of gum arabic and a range of carbohydrate wall materials (oil/gum = 0.5) were prepared and analyzed. Maize starch and glucose were ineffective as partial replacers of gum arabic, but maltodextrins of various dextrose equivalence values (5.5-38) successfully replaced 50% of the gum arabic. The microencapsulation efficiency of the gum arabic/maltodextrin stabilized powders was further increased by increasing total solids of the feed to the dryer and by increasing the atomizer nozzle diameter.

Biotechnology↗