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P J Kelly

Publications and source records attributed to P J Kelly.

At least 19 recordsLinked to original sources
PubMed2006

TopCount coupled to ultra-performance liquid chromatography for the profiling of radiolabeled drug metabolites in complex biological samples.

The recent commercial availability of small particle packed columns (<2microm) and associated instrumentation capable of withstanding the high pressures of such columns, has lead to an increase in the application of so called ultra-performance liquid chromatography (UPLC). It has recently been shown that the improved efficiency, resolution and peak capacity of these columns, when coupled to mass spectrometry, provides particular benefit for the identification of drug metabolites in complex biological samples. In this work, the ability of TopCount, a microplate scintillation counter, to act as a suitable radiodetection system for ultra-performance liquid chromatography methods is tested. TopCount, has innumerable benefits over more traditional on-line radioactivity flow detection methods, when dealing with the narrow peak widths and small peak volumes associated with the enhanced efficiency of sub-2microm columns. The system is tested for robustness and sensitivity, and then used to undertake successful metabolite profiling of actual samples, and the data compared to traditional HPLC with on-line radioactivity flow detector.

Animals↗
PubMed2006

Association between tPA therapy and raised early matrix metalloproteinase-9 in acute stroke.

BACKGROUND: Matrix metalloproteinase-9 (MMP9) is expressed in acute ischemic stroke and up-regulated by tissue plasminogen activator (tPA) in animal models. The authors investigated plasma MMP9 and its endogenous inhibitor, tissue inhibitor of metalloproteinase (TIMP1), in tPA-treated and -untreated stroke patients. METHODS: Nonstroke control subjects and consecutive ischemic stroke patients presenting within 8 hours of onset were enrolled. Blood was sampled within 8 hours and at 24 hours, 2 to 5 days and 4 to 6 weeks. MMP9 and TIMP1 were analyzed by ELISA and gel zymography. RESULTS: Fifty-two cases (26 tPA treated, 26 tPA untreated) and 27 nonstroke control subjects were enrolled. Hyperacute MMP9 was elevated in tPA-treated vs tPA-untreated patients (medians 43 vs 28 ng/mL; p = 0.01). tPA therapy independently predicted hyperacute MMP9 after adjustment for stroke severity, volume, and hemorrhagic transformation (p = 0.01). There was a trend toward lower hyperacute TIMP1 levels in tPA-treated vs tPA-untreated patients (p = 0.06). Hyperacute MMP9 was correlated to poor 3-month modified Rankin Scale outcome (r = 0.58, p = 0.0005). CONCLUSION: Tissue plasminogen activator independently predicted plasma matrix metalloproteinase-9 (MMP9) in the first 8 hours after human ischemic stroke. As MMP9 may be an important mediator of hemorrhagic transformation, alternative thrombolytic agents or therapeutic MMP9 inhibition may increase the safety profile of acute stroke thrombolysis.

Aged↗
PubMed2006

Orientation-dependent transparency of metallic interfaces.

As devices are reduced in size, interfaces start to dominate electrical transport, making it essential to be able to describe reliably how they transmit and reflect electrons. For a number of nearly perfectly lattice-matched materials, we calculate from first principles the dependence of the interface transparency on the crystal orientation. Quite remarkably, the largest anisotropy is predicted for interfaces between the prototype free-electron materials silver and aluminum, for which a massive factor of 2 difference between (111) and (001) interfaces is found.

Journal Article↗
PubMed2006

Postpartum hemorrhage in resource-poor settings.

Despite the strong interest of international health agencies, worldwide maternal mortality has not declined substantially over the past 10 years. Postpartum hemorrhage (PPH) is the most common cause of maternal death across the world, responsible for more than 25% of deaths annually. Although effective tools for prevention and treatment of PPH are available, most are not feasible or practical for use in the developing world where many births still occur at home with untrained birth attendants. Application of many available clinical solutions in rural areas would necessitate substantial changes in government infrastructure and in local culture and customs surrounding pregnancy and childbirth. Before treatment can be administered, prompt and accurate diagnosis must be made, which requires training and appropriate blood measurement tools. After diagnosis, appropriate interventions that can be applied in remote settings are needed. Many uterotonics known to be effective in reducing PPH in tertiary care settings may not be useful in community settings because they require refrigeration and/or skilled administration. Moreover, rapid transfer to a higher level of care must be available, a challenge in many settings because of distance and lack of transportation. In light of these barriers, low-technological replacements for treatments commonly applied in the developed-world must be utilized. Community education, improvements to emergency care systems, training for birth attendants, misoprostol, and Uniject have shown promise as potential solutions. In the short term, it is expedient to capitalize on practical opportunities that utilize the existing strengths and resources in each community or region in order to implement appropriate solutions to save the lives of women during childbirth.

Cause of Death↗
PubMed2005

The detection of malingering in memory performance: the sensitivity and specificity of four measures in a UK population.

OBJECTIVES: To investigate the validity of a clinical neuropsychological battery for the detection of malingering on tests of memory. METHODS: A simulated scenario design was developed to investigate the effectiveness of a battery of four neuropsychological tests in the detection of malingering; the Coin in the Hand Test (CIH), Autobiographical Memory Index (AMI), Rey I 5-Item Test (RIT),and the Wechsler Mental Control Test (MCT). The performances of patients with an acquired brain injury (N = 40) were compared with two groups of controls instructed either to simulate a head injury performance (N = 40) or do their best (N = 40). RESULTS: The CIH and MCT demonstrated good validity and displayed high sensitivity and specificity. The RIT and the AMI was relatively poor in distinguishing between simulators and patients. CONCLUSIONS: The sensitivity and specificity of all four tests to the detection of malingering has been assessed. Two of the tests the CIH and MCT would be useful as a quick and accurate screening tool for detecting malingering.

Adult↗
PubMed2005

Serosurvey for canine distemper virus exposure in dogs in communal lands in Zimbabwe.

Sera from 173 apparently healthy, unvaccinated dogs from 4 widely separated communal lands in Zimbabwe were tested by ELISA for antibodies against canine distemper virus. Overall, 82% were positive with high prevalences found in each communal land. The highest seroprevalence was in dogs between 1 and 2 years of age (91%; 49/54). These results show dogs in the communal lands of Zimbabwe are commonly exposed to canine distemper virus and that a substantial number survive infection. The role that the virus might play in the high mortality rate of the dog population on communal land warrants further investigation.

Age Factors↗
PubMed2005

A preliminary study to evaluate the immune responses induced by immunization of dogs with inactivated Ehrlichia canis organisms.

Ehrlichia canis is an intracellular pathogen that causes canine monocytic ehrlichiosis. Although the role of antibody responses cannot be discounted, control of this intracellular pathogen is expected to be by cell mediated immune responses. The immune responses in dogs immunized with inactivated E. canis organisms in combination with Quil A were evaluated. Immunization provoked strong humoral and cellular immune responses, which were demonstrable by Western blotting and lymphocyte proliferation assays. By Western blotting antibodies to several immunodominant E. canis proteins were detected in serum from immunized dogs and antibody titres increased after each immunization. The complement of immunogenic proteins recognized by the antisera were similar to those recognized in serum from infected dogs. Upon challenge with live E. canis, rapid anamnestic humoral responses were detected in the serum of immunized dogs and primary antibody responses were detected in the serum from control dogs. Following immunization, a lymphocyte proliferative response (cellular immunity) was detected in peripheral blood mononuclear cells (PBMNs) of immunized dogs upon stimulation with E. canis antigens. These responses were absent from non-immunized control dogs until after infection with live E. canis, when antigen specific-lymphocyte proliferation responses were also detected in the PBMNs of the control dogs. It can be thus concluded that immunization against canine monocytic ehrlichiosis may be feasible. However, the immunization regimen needs to be optimized and a detailed investigation needs to be done to determine if this regimen can prevent development of acute and chronic disease.

Animals↗
PubMed2004

Treatment of temporomandibular disorders by stabilising splints in general dental practice: results after initial treatment.

INTRODUCTION: Little is known about how effective general dental practitioners (GDPs) are in treating temporomandibular disorders (TMD). The overall aim of this study was to compare the lower stabilising splint (SS) with a non-occluding control (CS) for the management of TMD in general dental practice. METHOD: A total of 93 TMD patients attending 11 GDPs were randomly allocated to SS or CS. Diagnosis was according to International Headache Society Criteria. Outcome criteria included pain visual analogue scale (VAS), number of tender muscles, aggregate joint tenderness, inter-incisal opening, TMJ clicks and headaches. Splints were fitted one week after baseline and patients were followed-up every three weeks to three months; those not responding to CS after six weeks (< 50% VAS reduction) were crossed over to SS for a further three months. RESULTS: Documentation was returned from nine GDPs for 72 patients (38 for SS, 34 for CS). At six weeks, mean improvements were noted for all outcome criteria, but less so for clicking. There were no significant differences between splints [chi(2)]. Seventeen CS patients had < 50% VAS reduction and were provided with SS in the cross-over group. CS patients with >50% VAS reduction were significantly younger than CS patients who crossed-over (ANOVA, p=0.009) and had significantly less diagnoses of TMJ clicking (chi(2), p<0.05). At the conclusion of the trial 16 patients were referred for specialist management: 11 non-responders (< 50% VAS reduction), one of whom needed occlusal adjustment and five responders also needing occlusal adjustment. CONCLUSIONS: At six weeks SS gave similar relief to CS for all outcome criteria. Patients who crossed-over from CS to SS were more likely to be older and have clicking TMJs. At the end of treatment nine of 11 non-responders to SS had a diagnosis of disc displacement with reduction. However, 80% TMD patients were managed effectively by GDPs using splints for periods of up to five months.

Adult↗
PubMed2004

A review of bacterial pathogens in Ctenocephalides felis in New Zealand.

The cat flea, Ctenocephalides felis, is the recognised vector of Bartonella henselae, B. clarridgeiae and Rickettsia felis. Although these Gram-negative bacteria were only described in the last decade, they are already known to cause a variety of diseases in people, particularly children and the immunosuppressed. Such diseases include cat-scratch disease, bacillary angiomatosis, endocarditis, bacteraemia, encephalopathy, neuroretinitis, osteomyelitis and peliosis hepatis. Although most infections in cats and dogs appear to be subclinical, recent studies have provided growing evidence that the bartonellas can also cause serious problems in pets, including hepatitis, endocarditis, central nervous system (CNS) signs, lymphadenopathy, uveitis, cataracts and reproductive failure. In 2004, DNA of B. henselae, B. clarridgeiae and R. felis was demonstrated in cat fleas from New Zealand and pets and their owners in the country are thus at risk of infection. While flea control programmes have traditionally been advocated by veterinarians to prevent pruritus and tapeworms in pets, they should now also be recommended to prevent infections with the new flea-borne bacterial pathogens. To raise awareness of the organisms amongst veterinarians and animal health workers, this review describes: the biology of the organisms; clinical and laboratory features of infections in cats, dogs and people; diagnosis; and possible treatments and control of infections with these organisms.

Journal Article↗
PubMed2004

Do gene-environment interactions influence fasting plasma lipids? A study of twins.

BACKGROUND: The aims of this study were to determine the influence of smoking, alcohol consumption, physical activity and hormone replacement therapy (HRT) on lipids, independently of genetic factors, and to detect whether gene-environment interactions influence these associations. MATERIALS AND METHODS: Fasting plasma total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, apolipoproteins AI and B and lipoprotein(a) were measured in 685 female twins (96 monozygotic, 230 dizygotic pairs and 33 singletons). RESULTS: Smokers had higher triglyceride and lower HDL cholesterol levels than never-smokers (P < 0.001). After controlling for genetic influences, smoking accounted for 0.35 mmol L(-1) and 0.22 mmol L(-1) differences in triglyceride and HDL cholesterol levels, respectively (P < 0.005), remaining significant after excluding alcohol-discordant twin pairs. In a gene-environment interaction analysis, the association between smoking and triglycerides was exaggerated in subjects at high genetic risk of hypertriglyceridaemia (interaction P=0.04). All levels of alcohol consumption were associated with higher HDL cholesterol levels than abstinence, but only moderate alcohol consumers had lower LDL cholesterol and triglyceride levels. In monozygotic twins concordant for smoking, an alcohol intake > 10 units week(-1) accounted for a 0.32 mmol L(-1) difference in LDL cholesterol, independently of genetic effects (P=0.04). In postmenopausal women, those using HRT had 0.54 mmol L(-1) lower LDL cholesterol and 0.21 micromol L(-1) lower lipoprotein(a) levels than nonusers (P < 0.001 and P=0.04, respectively); these differences were attenuated after accounting for genetic effects in monozygotic twins. Although physically active subjects had higher levels of HDL cholesterol than nonactive subjects, this was nonsignificant after adjusting for genetic factors. CONCLUSIONS: Smoking-induced aberrations in HDL cholesterol and triglycerides and alcohol-related differences in LDL cholesterol were independent of genetic influences. The association between smoking and hypertriglyceridaemia was accentuated in high genetic risk individuals.

Adult↗
PubMed2004

Holter monitoring in the diagnosis of stroke mechanism.

BACKGROUND: Atrial fibrillation (AF), an important and treatable cause of ischaemic stroke, can occur as a sustained or a paroxysmal arrhythmia. Continuous cardiac rhythm monitoring (Holter monitoring) is often performed in stroke patients to identify paroxysmal AF, which is an indication for warfarin anti-coagulation in this patient population. AIM: The aim of this study was to assess the clinical utility of Holter monitoring in detecting occult AF in patients with possible cardioembolic stroke. METHODS: The medical records of ischaemic stroke patients consecutively hospitalized at a single academic centre during a one-year period were reviewed. Data regarding patient demographics, stroke characteristics, electrocardiography and echocardiography results and duration and findings of Holter monitoring were abstracted. The primary outcome was yield of newly diagnosed AF on Holter monitoring. RESULTS: Of 465 consecutive patients admitted with a diagnosis of new ischaemic stroke, 210 underwent Holter monitoring. The mean duration of monitoring was 22.8 +/- 4.0 h. Previously undiscovered AF was -identified in five cases (2.4%), all of which represented non-rheumatic AF. In three cases, the Holter test was negative despite AF documented on an admission electro-cardiogram. CONCLUSIONS: Holter monitoring can identify occult paroxysmal AF, assisting targeted secondary prevention in patients with new ischaemic stroke. However, the standard 24-h duration of monitoring probably under-estimates the prevalence of paroxysmal AF in this population. Prospective studies are indicated to evaluate the value of longer monitoring periods in stroke populations.

Aged↗
PubMed2004

Antibodies reactive with Bartonella henselae and Ehrlichia canis in dogs from the communal lands of Zimbabwe.

The prevalences of antibodies against Bartonella henselae and Ehrlichia canis were determined in sera from 228 dogs in 5 communal lands of Zimbabwe, areas where traditional subsistence agro-pastoralism is practised. The sera were collected from apparently healthy dogs during routine rabies vaccination programmes and tested with indirect fluorescent antibody assays using B. henselae (Houston-I) and E. canis (Oklahoma) as antigens. We found reactive antibodies (> or =1:80) against B. henselae in 14% of the dogs tested. Seropositive animals were found in Bikita (41%; 17/42), Omay (13%; 6/48), Chinamora (5%; 2/38) and Matusadona (15%; 7/48). No seropositive dogs were found in Chiredzi (0%; 0/52). Antibodies reactive with E. canis (> or =1:80) were found in 34% of the dogs tested, from Bikita (88%; 37/42), Chiredzi (31%; 16/52), Omay (17%; 8/48), Chinamora (26%; 10/38) and Matusadona (15%; 7/48). Our survey shows dogs in the communal lands of Zimbabwe are frequently exposed to E. canis and B. henselae or closely related species. Further studies are indicated to determine the pathogenicity of the organisms infecting these dogs and their clinical significance.

Age Factors↗
PubMed2003

Inflammation, homocysteine, and vitamin B6 status after ischemic stroke.

BACKGROUND AND PURPOSE: Epidemiological studies have described an association between low vitamin B6 (measured as pyridoxal 5'-phosphate [PLP]) and ischemic stroke, independent of homocysteine (tHcy). We investigated B6 status, tHcy, and inflammation (measured by C-reactive protein [CRP]) in patients with stroke and controls. METHODS: Consecutive cases with new ischemic stroke were compared with matched controls. Fasting tHcy, PLP, and CRP were measured. RESULTS: The adjusted odds ratio of low PLP in the highest compared with the lowest CRP quartile was 16.6 (2, 139.9, P=0.01). Age, CRP, supplemental vitamin use, and albumin were independent predictors of PLP (P<0.05 for all). No relationship was observed between CRP and tHcy. CONCLUSIONS: The relationship between inflammation and low B6 status may partially explain the findings of previous epidemiological studies.

Aged↗
PubMed2003

Stroke in young patients with hyperhomocysteinemia due to cystathionine beta-synthase deficiency.

BACKGROUND: Although hyperhomocyst(e)inemia (Hyper-Hcy) may predispose to atherosclerosis and venous thrombosis, the mechanisms of stroke associated with Hyper-Hcy are not defined. METHODS: Clinical and biochemical phenotypes and genetic features of three unrelated patients with premature stroke and severe Hyper-Hcy due to cystathionine beta-synthase (CBS) deficiency are described. Plasma Hcy and amino acids were measured by fluorescence polarization immune assay and ion exchange chromatography. Analysis of the CBS and methylenetetrahydrofolate reductase genes was performed by restriction enzyme digestion and sequence analysis. RESULTS: Two of the three index cases had no known diagnosis of homocystinuria and initially presented with embolic cerebral and retinal infarction in mid-adulthood. Mechanisms of cerebrovascular disease were carotid intraluminal thrombosis, arterial dissection, and possible cardiac embolism. Family screening revealed additional members with clinically silent homocystinuria and severe Hyper-Hcy. Excluding tall stature in two individuals, all had mild phenotypes, without classic findings of CBS deficiency. Plasma total and free Hcy, methionine, and urine Hcy were elevated. Genotyping revealed heterozygous CBS mutations (I278T, D444N, G307S) in affected individuals. CONCLUSION: Artery-to-artery embolism and dissection may cause stroke in young adults with homocystinuria. The results also support a rationale for screening for Hyper-Hcy in young adults with stroke without a phenotype suggestive of classic homocystinuria.

Adolescent↗
PubMed2002

Spin-dependent transparency of ferromagnet/superconductor interfaces.

We combine parameter-free calculations of the transmission and reflection matrices for clean and dirty interfaces with a scattering-theory formulation of Andreev reflection (AR) generalized to spin-polarized systems in order to critically evaluate the use of an extended Blonder-Tinkham-Klapwijk (BTK) model to extract values of the spin polarization for ferromagnetic metals from measurements of point-contact AR. Excellent agreement with the experimental conductance data is found for Pb/Cu but it is less good for Pb/Ni and poor for Pb/Co, indicating that the BTK formalism does not describe transport through superconducting/ferromagnetic interfaces correctly.

Journal Article↗
PubMed2002

Homocysteine, MTHFR 677C-->T polymorphism, and risk of ischemic stroke: results of a meta-analysis.

BACKGROUND: Data are conflicting concerning risk for ischemic stroke associated with hyperhomocyst(e)inemia (hyper-Hcy) and a common polymorphism in the gene encoding 5,10-methylenetetrahydrofolate reductase (MTHFR 677C-->T), which predisposes to hyper-Hcy in vivo. METHODS: Search of MEDLINE, Science Citation Index, and abstracts of conference proceedings revealed relevant articles. Exposure was defined as follows: 1) prevalence of hyper-Hcy; 2) absolute difference in the mean Hcy concentration between subjects with and without ischemic stroke; and 3) the MTHFR TT genotype frequency. Outcome was defined as ischemic stroke with or without neuroimaging. Inclusion criteria were retrospective and prospective studies with reported odds ratios (OR) or hazard ratios (HR) or arithmetic mean Hcy levels. Exclusion criteria were absence of OR or HR, outcome defined as carotid atherosclerosis or intima-media thickening, stroke in patients younger than 18 years old, and studies in languages other than English. Statistical analyses for between-study heterogeneity and pooled risk estimates were performed using Stata software (Stata Corporation, College Station, TX). RESULTS: Among 16 studies (1,487 stroke and 2,554 nonstroke cases), the pooled mean Hcy level in patients with ischemic stoke was 2.32 micromol/L (95% CI, 1.6 to 3.04; p < 0.001) greater than that in those without ischemic stroke. Among 14 included studies (1,769 stroke and 7,400 nonstroke cases), the pooled OR estimate of ischemic stroke associated with hyper-Hcy was 1.79 (95% CI, 1.61 to 2.0; p < 0.001). Among 19 included studies (2,788 stroke and 3,962 nonstroke cases), the OR associated with the TT genotype was 1.23 (95% CI, 0.96 to 1.58; p = 0.1). CONCLUSION: These data support an association between mild-to-moderate hyper-Hcy and ischemic stoke. The MTHFR TT genotype may have a small influence in determining susceptibility to ischemic stoke.

Brain Ischemia↗