Search PubMed⌕ Search

Biomedical subjects

A J Morris

Publications and source records attributed to A J Morris.

At least 37 records · Page 2Linked to original sources
PubMed2003

Hepatic granulomas: a 10 year single centre experience.

BACKGROUND: Epithelioid granulomas have been reported in 2-15% of unselected liver biopsies, with numerous underlying aetiologies described. However, all UK series were reported before identification of hepatitis C virus (HCV). AIM: To evaluate the current aetiologies of hepatic granulomas and to assess the prognosis for the "idiopathic" group, in which all investigations for a recognised cause were negative or normal. METHODS: A retrospective review of patient case notes between 1991 and 2001; all patients who had a liver biopsy at Glasgow Royal Infirmary revealing epithelioid granulomas had their case notes and liver biopsies reviewed and a standard proforma completed. RESULTS: Over the study period, 1662 liver biopsies were performed. Hepatic granulomas were found in 63. Of those identified, 47 were female, with a mean age of 42 years (range, 17-81). Underlying aetiologies were as follows: primary biliary cirrhosis (PBC; 23.8%), sarcoidosis (11.1%), idiopathic (11.1%), drug induced (9.5%), HCV (9.5%), PBC/autoimmune hepatitis (AIH) overlap (6.3%), Hodgkin lymphoma (6.3%), AIH (4.8%), tuberculosis (4.8%), resolving biliary obstruction (3.2%), and other single miscellaneous causes (9.5%). Of the seven patients with idiopathic hepatic granulomas, one was lost to follow up, one died of stroke, and the remaining five were well with no liver related morbidity at a mean follow up of 6.2 years. CONCLUSIONS: The aetiology of hepatic granulomas is broad ranging, with HCV an important cause in this population. Despite extensive investigations, a 10-15% of patients still had "idiopathic" hepatic granulomas. However, the prognosis for this last group appears to be excellent.

Adolescent↗
PubMed2002

Enhanced bio-manufacturing through advanced multivariate statistical technologies.

The paper describes the interrogation of data, from a reaction vessel producing an active pharmaceutical ingredient (API), using advanced multivariate statistical techniques. Due to the limited number of batches available, data augmentation was used to increase the number of batches thereby enabling the extraction of more subtle process behaviour from the data. A second methodology investigated was that of multi-group modelling. This allowed between cluster variability to be removed, thus allowing attention to focus on within process variability. The paper describes how the different approaches enabled the realisation of a better understanding of the factors causing the onset of an impurity formation to be obtained as well demonstrating the power of multivariate statistical data analysis techniques to provide an enhanced understanding of the process.

Artifacts↗
PubMed2002

Limited diversity among human isolates of Bartonella henselae.

A study of 59 isolates of Bartonella henselae reveals relatively limited diversity among those of human origin (n = 28). Either of two distinct alleles of both gltA and 16S ribosomal DNA (rDNA) was found in all isolates, with a high level of congruity between 16S and gltA inheritance among proven human pathogens. Human isolates from all over Eastern Australia were most commonly 16S rDNA (Bergmans) type I, with the same gltA allele as the type strain (Houston-1). Comparable feline isolates were more commonly 16S type II, with less congruity of inheritance between 16S and gltA alleles. Previously described arbitrarily primed PCR and EagI-HhaI infrequent restriction site PCR fingerprinting techniques separated Bartonella species effectively but lacked discriminating power within B. henselae. Examination of the 16-23S intergenic spacer region revealed for several strains several point mutations as well as a repeat sequence of unknown significance which is readily detected by HaeIII restriction fragment length polymorphism analysis. The bacteriophage-associated papA gene was present in all isolates. Enterobacterial repetitive intergenic consensus PCR proved to be a useful and robust typing tool and clearly separated human isolates (including imported strains) from the majority of feline isolates. Our data are consistent with published evidence and with previous suggestions of intragenomic rearrangements in the type strain and suggest that human isolates come from a limited subset of B. henselae strains. They strengthen arguments for careful exploration of genotype-phenotype relationships and for the development of a multilocus enzyme electrophoresis and multilocus sequence typing-based approach to the phylogeny of B. henselae.

Animals↗
PubMed2002

Helicobacter pylori eradication for peptic ulceration: an observational study in a Scottish primary care setting.

Despite being established for the treatment of peptic ulcer (PU) disease, few studies have assessed the long-term effectiveness and economic benefits of Helicobacter pylori (Hp) eradication in primary care. Our aim was to investigate the effect of community based Hp eradication for patients with chronic peptic ulcer disease requiring maintenance acid suppression. The endpoints used were the patients dyspeptic symptoms and the requirement for the prescription of maintenance acid suppression therapy. The study area covered seven general practices in the Glasgow area. Patients with previously diagnosed peptic ulcer disease receiving prescribed acid suppression therapy were invited to a dyspepsia clinic. Hp status was assessed by Helisal rapid blood test (HRBT). Positive patients received Hp eradication therapy and were reviewed six weeks later. At six months a review of practice records was carried out, and two years after eradication a postal questionnaire was sent to participating patients. A total of 243 patients attended the initial clinic of which 81.9% were HRBT positive. 156 of 196 patients offered Hp eradication re-attended at six weeks. The per protocol eradication rate was 91.7%. After six months patients who had received eradication therapy were less likely to require maintenance acid suppression therapy compared with those to whom eradication was not given. Two years after treatment 76.5% of patients felt their symptoms were improved, but 42.2% were still receiving maintenance therapy. The estimated cost of treatment per month per patient had fallen from 20.23 Pounds to 9.39 Pounds after eradication. In conclusion we felt that community based Hp eradication for patients with chronic PU disease is effective, however it does not completely alleviate dyspepsia. Predictors of symptomatic response or of no longer requiring acid suppression therapy after two years were younger age of onset of PU disease and absence of pre-documented gastro-oesophageal reflux disease or hiatus hernia. Hp eradication improves patients symptoms, reduces the requirement for maintenance acid suppression and is cost-effective after two years follow-up in this targeted group.

Female↗
PubMed2001

Primary and secondary dental care: the nature of the interface.

Specialist dental services are scarce resources and are often oversubscribed. A key element is how these services relate to their referral base, in other words the interface between primary and secondary dental care. Dentistry has several unique qualities when compared with medicine and the nature of the interface between primary and secondary dental care is consequently very different to the medical interface, whilst apparently sharing common features. This paper examines the nature of that interface, the drivers for patient flow between services and outlines the properties of an ideal interface. This model can then be used as a way of describing some of the problems facing specialist dental services and of assessing any proposed solutions.

Continuity of Patient Care↗
PubMed2001

Primary and secondary dental care: how ideal is the interface?

In our previous paper in this journal, we described an ideal interface between primary and secondary dental care in terms of equity, seamless care and efficiency and effectiveness. This paper examines the published evidence describing considerable ongoing problems with the interface under these headings and the ways in which those problems might be better described, quantified and addressed.

Continuity of Patient Care↗
PubMed2001

Role of Src kinase in diperoxovanadate-mediated activation of phospholipase D in endothelial cells.

We have shown earlier that oxidant-induced activation of phospholipase D (PLD) in vascular endothelial cells (ECs) is regulated by protein tyrosine kinases. To further understand the regulation of oxidant-induced PLD activation, we investigated the role of Src kinase. Treatment of bovine pulmonary artery ECs (BPAECs) with a model oxidant, diperoxovanadate (DPV), at 5 microM concentration, for 30 min, stimulated PLD activity (four- to eightfold), which was attenuated by tyrosine kinase inhibitors and by Src kinase-specific inhibitors PP-1 and PP-2, in a dose- and time-dependent fashion. Furthermore, BPAECs exposed to DPV (5 microM) for 2 min showed activation of Src kinase as observed by increased tyrosine phosphorylation and autophosphorylation in Src immunoprecipitates, which was attenuated by PP-2. Src immunoprecipitates of cell lysates from control BPAECs exhibited PLD activity in cell-free preparations, which was Arf- and Rho-sensitive and was enhanced at 2 min of DPV (5 microM) treatment. Also, Western blots of Src immunoprecipitates of control cells revealed the presence of PLD(1) and PLD(2), suggesting the association of PLD with Src kinase under basal conditions. However, exposure of cells to DPV (5 microM) for 2 min enhanced the association of PLD(2) but not PLD(1) with Src. Western blotting of immunoprecipitates of PLD(1) and PLD(2) isoforms of control BPAECs revealed the presence of Src under basal conditions and exposure of cells to DPV (5 microM) for 2 min enhanced the association of PLD(2) with Src in PLD(2) immunoprecipitates. Transient expression of a dominant negative mutant of Src in BPAECs attenuated DPV- but not TPA-induced PLD activation. In cell-free preparations, Src did not phosphorylate either PLD(1) or PLD(2) compared to protein kinase Calpha or p38 mitogen-activated protein kinase. These data show for the first time a direct association of Src with PLD in ECs and regulation of PLD in intact cells.

Animals↗
PubMed2001

Ceramide inhibition of mammalian phospholipase D1 and D2 activities is antagonized by phosphatidylinositol 4,5-bisphosphate.

Ceramides inhibit phospholipase D (PLD) activity in several mammalian cell types. These effects have been related to preventing activation by ARF1, RhoA, and protein kinase C-alpha and -beta and therefore indicate that PLD1 is inhibited. In the present work, we investigated the effects of ceramides in inhibiting both PLD1 and PLD2 and the interaction with another activator, phosphatidylinositol 4,5-bisphosphate (PIP2). PLD1 and PLD2 were overexpressed separately in Sf9 insect cells using baculovirus vectors. In our cell-free system, PLD1 activity was inhibited completely by C2-ceramide at sub-optimum concentrations of PIP2 (3 and 6 microM), whereas at supra-optimum PIP2 concentrations (18 and 24 microM) C2-ceramide did not inhibit PLD1 activity. Partially purified PLD2 exhibited an absolute requirement for PIP2 when the activity was measured using Triton X-100 micelles. Ceramides inhibited PLD2 activity, and this inhibition was decreased as PIP2 concentrations increased. However, C2-ceramide also reversibly inhibited the activity of PLD1 and PLD2 mutants in which binding of PIP2 was decreased, indicating that ceramides are interacting with the catalytic core of the mammalian PLDs. By contrast, C2-ceramide failed to produce a significant inhibition of PLDs from bacteria and plants. Our results provide a novel demonstration that ceramides reversibly inhibit mammalian PLD2 as well as PLD1 activities and that both of these actions are more pronounced when PIP2 concentrations are rate-limiting.

Bacterial Proteins↗
PubMed2001

The oral cleanliness and periodontal health of UK adults in 1998.

Periodontal disease continues to be a major concern for dentists and patients. This paper reports the findings of the 1998 UK Adult Dental Health survey in relation to plaque, calculus, periodontal pocketing and loss of attachment. It is apparent from this study that moderate periodontal disease remains commonplace amongst UK adults and that the associated risk factors of plaque and calculus are in abundance, even amongst those who profess to be motivated about their oral health and attend the dentist regularly. The continued high prevalence of disease needs to be seen in the context of the far larger number of people who are now potentially at some risk, particularly in the older age groups, because of improvements in tooth retention. However, the cumulative effect of disease means that control of the periodontal diseases, even mild and slowly progressing disease, will be a key issue if large numbers of teeth are to be retained into old age. If that level of control is to be achieved we need a widespread improvement in our management of the disease, particularly in our ability to improve the oral cleanliness of the UK population.

Adolescent↗
PubMed2001

Selective induction of phospholipase D1 in pathogen-activated human monocytes.

Phospholipase D (PLD) activation is part of the complex signalling cascade induced during phagocyte activation. Two PLD isoforms have been cloned, but their role in phagocyte functions is still poorly defined. We report that resting fresh circulating human monocytes expressed PLD1. PLD1 protein expression was rapidly down-regulated during cell culture. Lipopolysaccharide and pathogen-derived agonists (Candida albicans, arabinoside-terminated lipoarabinomannan and Gram-positive bacteria, but not mannose-capped lipoarabinomannan or double-stranded RNA) strongly induced PLD1 expression at both the mRNA and protein levels. Pro-inflammatory cytokines [interleukin (IL)-1beta and tumour necrosis factor alpha] had only a weak effect, whereas immune cytokines (IL-6 and interferon gamma), anti-inflammatory cytokines (IL-13 and IL-10) and chemoattractants (fMet-Leu-Phe and macrophage chemoattractant protein 1) were inactive. None of the agonists tested induced significant changes in the basal expression of PLD2 mRNA. Consistent with PLD1 up-regulation was the observation that PLD enzymic activity was higher in monocytes treated with active-pathogen-derived agonists than in control cells, when stimulated with PMA or with chemotactic agonists (fMet-Leu-Phe and C5a). Thus PLD2 seems to be a constitutive enzyme in circulating monocytes. Conversely, PLD1 is an inducible protein, rapidly regulated during culture conditions and selectively induced during cell activation. Therefore PLD1 might have a relevant role in immune responses against pathogens and in chronic inflammation.

Blotting, Northern↗
PubMed2001

Pneumococcal bacteraemia and opportunities for prevention.

AIMS: Despite availability of active antimicrobial agents for its treatment, the mortality from pneumococcal bacteraemia (PB) may reach 30% to 40% in high-risk groups. Greater vaccine use may reduce the incidence of PB. The aim of this study was to determine the proportion of patients with PB who had indications for, but had not received, pneumococcal vaccination. METHODS: From December 1998 to March 2000, all episodes of PB in adults in four Auckland hospitals were followed prospectively. Underlying disease, outcome, and pneumococcal vaccination history were recorded. RESULTS: 96 patients had PB: the median age was 63 years, range 16 to 93 years. 42 (44%) were > or = 65 years. The relative risk (RR) of acquiring PB for Maori and Pacific Island people was more than two times that of both European and other ethnic groups: RR 2.3 (95% CI 1.5 - 3.6) and 2.4 (1.6 - 3.8), respectively. The most common presentation was pneumonia; 84 (88%), of which 74 (88%) were community acquired. Five (5%) patients had meningitis. The overall mortality was 18%. Eleven (11%) pneumococcal isolates had intermediate susceptibility to penicillin and six (6%) were resistant. 69 (72%) patients had one or more condition for which pneumococcal vaccination is recommended but only two (2%) patients had received it. 82 (85%) patients were infected with serotypes included in the current pneumococcal vaccine. CONCLUSIONS: Most adult patients with PB have underlying medical conditions for which vaccination is recommended but only rare patients get vaccinated. Emerging antimicrobial resistance is a further incentive to increase the use of pneumococcal vaccination. Greater use of pneumococcal vaccine will probably require a change in its funding status, similar to the current policy for influenza vaccine. It may also be appropriate to consider targeted use of the vaccine in Maori and Pacific Island people given their higher rates of disease.

Adolescent↗
PubMed2001

Phospholipase D1: a key factor for the exocytotic machinery in neuroendocrine cells.

Phospholipase D (PLD) has been proposed to mediate cytoskeletal remodeling and vesicular trafficking along the secretory pathway. We recently described the activation of an ADP ribosylation factor-regulated PLD at the plasma membrane of chromaffin cells undergoing secretagogue-stimulated exocytosis. We show here that the isoform involved is PLD1b, and, using a real-time assay for individual cells, that PLD activation and exocytosis are closely correlated. Moreover, overexpressed PLD1, but not PLD2, increases stimulated exocytosis in a phosphatidylinositol 4,5-bisphosphate-dependent manner, whereas catalytically inactive PLD1 inhibits it. These results provide the first direct evidence that PLD1 is an important component of the exocytotic machinery in neuroendocrine cells.

Actins↗
PubMed2001

Dental attitudes and behaviours in 1998 and implications for the future.

The 1998 Adult Dental Health Survey included face to face interviews with participants to determine their dental attitudes and behaviours. This article considers reported oral hygiene practices, treatment choices, satisfaction with appearance of teeth, attitudes towards wearing dentures and how these have changed since previous surveys. Although overall there has been a steady improvement in dental health attitudes, adults from disadvantaged households are still lagging behind. This has implications for social equity.

Adult↗
PubMed2001

Potent direct inhibition of mammalian phospholipase D isoenzymes by calphostin-c.

Calphostin-c inhibits protein kinase C (PKC) isoenzymes by covalent modification of the lipid binding regulatory domain. Exposure of cells to calphostin-c elicits PKC independent effects including disruption of intracellular transport, growth inhibition, and stimulation of apoptosis suggesting actions at additional targets. Phospholipase D (PLD) enzymes are targets for activation by PKC. We have investigated the PKC isoenzyme selectivity for activation of two mammalian PLD enzymes, PLD1 and PLD2, by PKC. We examined the sensitivity of this process to widely used PKC inhibitors and report the surprising finding that calphostin-c is a potent direct inhibitor of PLD1 and PLD2. In vitro, calphostin-c inhibits activity of both PLD1 and PLD2 with an IC(50) of approximately 100 nM. Inhibition is not overcome by protein and lipid activators of these enzymes and does not involve blockade of phosphatidylinositol 4,5-bisphosphate-dependent PLD binding to substrate containing liposomes. Studies using a series of deletion and point mutants of the enzymes suggest that calphostin-c targets the PLD catalytic domain. Inhibition of PLD by calphostin-c in vitro involves stable and apparently irreversible modification of the enzyme. Activity of both PLD1 and PLD2 can be inhibited by calphostin-c treatment of intact cells in a manner that is independent of upstream actions of PKC. Our results suggest that inhibition of PLD1 and PLD2 may explain some of the PKC-independent effects of calphostin-c observed when the compound is applied to intact cells.

Animals↗
PubMed2001

Infection of orthopedic prostheses after Staphylococcus aureus bacteremia.

We prospectively evaluated 53 patients with prosthetic joints and 27 patients with other orthopedic prosthetic devices who developed Staphylococcus aureus bacteremia (SAB). After exclusion of patients with primary postoperative infections, the risk of a prosthesis becoming infected by means of hematogenous seeding after SAB was 34% (15 of 44 patients) for prosthetic joints and 7% (1 of 15 patients) for other orthopedic prostheses.

Adult↗
PubMed2001

Identification of Yersinia-infected blood donors by anti-Yop IgA immunoassay.

BACKGROUND: From 1991 through 1996, nine transfusion-related cases of septicemia and endotoxemia occurred in New Zealand, a rate approximately 80 times that in the United States. Eight cases involved the transfusion of Yersinia enterocolitica-infected blood and one involved Serratia liquefaciens-infected blood. Six of the recipients died. Donor exclusion by recent gastrointestinal illness failed to prevent the four most recent such infections, and it has led to an estimated 3- to 5-percent rate of donor deferral. STUDY DESIGN AND METHODS: An antigen preparation containing the released proteins (Yops) of Y. enterocolitica was used to establish an EIA to detect IgA directed against these proteins in donated blood. The assay was tested with serum from donors in transfusion-related endotoxemia cases, subjects who were stool culture-positive for Y. enterocolitica, and 495 healthy volunteer blood donors. RESULTS: The assay detected anti-Yop IgA in the donors of all 6 infected units tested. Ninety-six percent of culture-positive subjects tested positive, whereas there was 70-percent positivity with a commercial immunoassay based on lipopolysaccharide. Five percent of random donors tested positive; only one of these had Y. enterocolitica present in a stool sample, and none were bacteremic. CONCLUSION: The anti-Yop immunoassay used in this study could be applied to reduce the risk of posttransfusion endotoxic shock caused by Y. enterocolitica.

Bacterial Proteins↗