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1.
JPRAS Open ; 37: 42-51, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37360978

ABSTRACT

Background/Aim: NovoSorbⓇ Biodegradable Temporizing Matrix (BTM) is a relatively novel, biodegradable polyurethane-based dermal regeneration template. The aim of this study was to evaluate the long-term scarring outcomes and safety of BTM in patients who underwent dermal reconstruction involving ≥5% of the total body surface area. Methods: This was a postmarket, multicenter, observational cohort study involving evaluation of long-term outcomes in patients treated with BTM. A total of 55 patients (35 from Royal Adelaide Hospital, South Australia, and 20 from Victoria Adult Burns Service, The Alfred, Victoria) who underwent dermal repair with BTM between 2011 and 2017 were screened for inclusion in this study. All patients had BTM implanted for ≥18 months. Results: Fifteen eligible patients with a mean (SD) age of 49.1 (14.3) years completed study assessments. These patients had a total of 39 areas treated with BTM. Using the Patient and Observer Scar Assessment Scale, scar quality was reported to be good by both observers and patients, with a mean (SD) observer score across all lesions of 3.6 (1.2) and mean (SD) overall opinion of 3.8 (1.2) as well as a mean (SD) patient score of 3.5 (1.2) and overall opinion of 5.0 (2.2). No adverse events or adverse device effects were reported or identified. Conclusion: The long-term scar quality is comparable to published studies. BTM is safe in the long term with no additional risks or adverse consequences being identified.

2.
J Hand Surg Am ; 45(10): 909-917, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32690338

ABSTRACT

PURPOSE: Distal radioulnar joint (DRUJ) instability may occur after an injury, resulting in pain and reduced strength. When primary repair is not possible or initial fixation has failed, chronic instability may result, requiring a reconstructive procedure such as the Adams procedure. The first purpose of this study was to evaluate the role of the triangular fibrocartilage complex and various components of the interosseous membrane as they were sectioned. The second purpose was to evaluate the Adams procedure in stabilizing the forearm. METHODS: Eight fresh cadaver forearms were dynamically moved through an average range of 56.8° pronation to 54.8° supination and tested first with the forearm intact and then after sectioning each of the following structures: the dorsal (DRUL) and palmar radioulnar ligaments (PRUL), the distal interosseous membrane, and the central band. Finally, they were tested after reconstruction using the Adams procedure. During each forearm motion and provocative shuck, the motion of the radius and ulna were measured and the locations of the radial attachments of the DRUL, PRUL, and sigmoid notch and ulnar fovea were computed. RESULTS: Significant increases in the gap between the ulnar fovea and the attachment sites of the DRUL and PRUL were observed with incremental sectioning, most notably after sectioning of the central band. Reconstruction significantly reduced the gap at the DRUL and PRUL sites during dynamic motion. CONCLUSIONS: This study reinforces the concept that DRUJ stability depends on more than the radioulnar ligaments, ulnocarpal ligaments, and triangular fibrocartilage complex, but is also significantly affected by the distal and central interosseous membrane. Reconstruction reduces gapping. CLINICAL RELEVANCE: These results suggest that the Adams reconstruction is a reasonable option to address DRUJ instability but may be an incomplete solution in the setting of a ruptured interosseous ligament.


Subject(s)
Joint Instability , Biomechanical Phenomena , Cadaver , Humans , Joint Instability/surgery , Pronation , Radius , Supination , Ulna , Wrist Joint/surgery
3.
medRxiv ; 2020 May 19.
Article in English | MEDLINE | ID: mdl-32511486

ABSTRACT

IMPORTANCE: The novel Coronavirus Disease 2019 (COVID-19), declared a pandemic in March 2020, may present with disproportionately higher rates in underrepresented racial/ethnic minority populations in the United States, including African American communities who have traditionally been over-represented in negative health outcomes. STUDY OBJECTIVE: To understand the impact of the density of African American communities (defined as the percentage of African Americans in a county) on COVID-19 prevalence and death rate within the three most populous counties in each U.S. state and territory (n=152). Design: An ecological study using linear regression was employed for the study. SETTING: The top three most populous counties of each U.S. state and territory were included in analyses for a final sample size of n=152 counties. PARTICIPANTS: Confirmed COVID-19 cases and deaths that were accumulated between January 22, 2020 and April 12, 2020 in each of the three most populous counties in each U.S. state and territory were included. MAIN OUTCOME MEASURES: Linear regression was used to determine the association between African American density and COVID-19 prevalence (defined as the percentage of cases for the county population), and death rate (defined as number of deaths per 100,000 population). The models were adjusted for median age and poverty. RESULTS: There was a direct association between African American density and COVID-19 prevalence; COVID-19 prevalence increased 5% for every 1% increase in county AA density (p<.01). There was also an association between county AA density and COVID-19 deaths, such; the death rate increased 2 per 100,000 for every percentage increase in county AA density (p=.02). CONCLUSION: These study findings indicate that communities with a high African American density have been disproportionately burdened with COVID-19. Further study is needed to indicate if this burden is related to environmental factors or individual factors such as types of employment or comorbidities that members of these community have.

4.
Nat Chem ; 9(1): 17-25, 2017 01.
Article in English | MEDLINE | ID: mdl-27995921

ABSTRACT

Synthetic control over pore size and pore connectivity is the crowning achievement for porous metal-organic frameworks (MOFs). The same level of control has not been achieved for molecular crystals, which are not defined by strong, directional intermolecular coordination bonds. Hence, molecular crystallization is inherently less controllable than framework crystallization, and there are fewer examples of 'reticular synthesis', in which multiple building blocks can be assembled according to a common assembly motif. Here we apply a chiral recognition strategy to a new family of tubular covalent cages to create both 1D porous nanotubes and 3D diamondoid pillared porous networks. The diamondoid networks are analogous to MOFs prepared from tetrahedral metal nodes and linear ditopic organic linkers. The crystal structures can be rationalized by computational lattice-energy searches, which provide an in silico screening method to evaluate candidate molecular building blocks. These results are a blueprint for applying the 'node and strut' principles of reticular synthesis to molecular crystals.

5.
Genom Data ; 5: 268-271, 2015 Sep 01.
Article in English | MEDLINE | ID: mdl-26251825

ABSTRACT

Amyloid-ß (Aß) peptides accumulate in the brains of patients with Alzheimer's disease (AD), where they generate a persistent inflammatory response from microglia, the innate immune cells of the brain. The immune modulatory cyclooxygenase/prostaglandin E2 (COX/PGE2) pathway has been implicated in preclinical AD development, both in human epidemiology studies1 and in transgenic rodent models of AD2, 3. PGE2 signals through four G-protein-coupled receptors, including the EP2 receptor that has been investigated for its role in mediating the inflammatory and phagocytic responses to Aß4. To identify transcriptional differences in microglia lacking the EP2 receptor, we examined mice with EP2 conditionally deleted in Cd11b-expressing immune cells. We injected Aß peptides or saline vehicle into the brains of adult mice, isolated primary microglia, and analyzed RNA expression by microarray. The resulting datasets were analyzed in two studies5, 6, one describing the basal status of microglia with or without EP2 deletion, and the second study analyzing the microglial response to Aß. Here we describe in detail the experimental design and data analyses. The raw data from these studies are deposited in GEO, accession GSE57181 (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE57181).

6.
J Clin Invest ; 125(1): 350-64, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25485684

ABSTRACT

Microglia, the innate immune cells of the CNS, perform critical inflammatory and noninflammatory functions that maintain normal neural function. For example, microglia clear misfolded proteins, elaborate trophic factors, and regulate and terminate toxic inflammation. In Alzheimer's disease (AD), however, beneficial microglial functions become impaired, accelerating synaptic and neuronal loss. Better understanding of the molecular mechanisms that contribute to microglial dysfunction is an important objective for identifying potential strategies to delay progression to AD. The inflammatory cyclooxygenase/prostaglandin E2 (COX/PGE2) pathway has been implicated in preclinical AD development, both in human epidemiology studies and in transgenic rodent models of AD. Here, we evaluated murine models that recapitulate microglial responses to Aß peptides and determined that microglia-specific deletion of the gene encoding the PGE2 receptor EP2 restores microglial chemotaxis and Aß clearance, suppresses toxic inflammation, increases cytoprotective insulin-like growth factor 1 (IGF1) signaling, and prevents synaptic injury and memory deficits. Our findings indicate that EP2 signaling suppresses beneficial microglia functions that falter during AD development and suggest that inhibition of the COX/PGE2/EP2 immune pathway has potential as a strategy to restore healthy microglial function and prevent progression to AD.


Subject(s)
Alzheimer Disease/metabolism , Microglia/immunology , Receptors, Prostaglandin E, EP2 Subtype/metabolism , Signal Transduction , Alzheimer Disease/immunology , Amyloid beta-Peptides/metabolism , Animals , Cells, Cultured , Chemokines/genetics , Chemokines/metabolism , Chemotaxis/immunology , Dinoprostone/physiology , Female , Gene Expression , Hippocampus/immunology , Hippocampus/pathology , Male , Mice, Inbred C57BL , Mice, Transgenic , Peptide Fragments/metabolism , Plaque, Amyloid/immunology , Presynaptic Terminals/metabolism , Spatial Memory , Transcriptome
7.
J Laryngol Otol ; 128(8): 720-4, 2014 Aug.
Article in English | MEDLINE | ID: mdl-25051340

ABSTRACT

OBJECTIVE: To analyse trends in two-week rule referrals for head and neck cancer over 10 years. METHOD: Data from two-week referrals received by the Wirral University Hospital NHS Trust between 1 January and 30 June 2012 were compared with similar data from 2002. RESULTS: A total of 357 referrals were received during the 6-month audit period, compared with 149 during the whole of 2002. Cancer pick-up rates were 9 per cent and 5 per cent in the first and second cycles, respectively. CONCLUSION: The annual number of two-week referrals made to our department increased by over 450 per cent in 10 years, but the resulting cancer pick-up rate fell by nearly 50 per cent. Whilst cancer patients need to be seen quickly, the current system is inefficient in parts. Modifications to the treatment pathway should be considered to improve patient care quality and reduce pressure on ENT departments.


Subject(s)
Clinical Audit/methods , Head and Neck Neoplasms/diagnosis , Referral and Consultation , Adult , Aged , Aged, 80 and over , Female , Guideline Adherence , Hospitals, General , Humans , Male , Middle Aged
8.
J Neurosci ; 33(40): 16016-32, 2013 Oct 02.
Article in English | MEDLINE | ID: mdl-24089506

ABSTRACT

Prostaglandin E2 (PGE2), a potent lipid signaling molecule, modulates inflammatory responses through activation of downstream G-protein coupled EP(1-4) receptors. Here, we investigated the cell-specific in vivo function of PGE2 signaling through its E-prostanoid 2 (EP2) receptor in murine innate immune responses systemically and in the CNS. In vivo, systemic administration of lipopolysaccharide (LPS) resulted in a broad induction of cytokines and chemokines in plasma that was significantly attenuated in EP2-deficient mice. Ex vivo stimulation of peritoneal macrophages with LPS elicited proinflammatory responses that were dependent on EP2 signaling and that overlapped with in vivo plasma findings, suggesting that myeloid-lineage EP2 signaling is a major effector of innate immune responses. Conditional deletion of the EP2 receptor in myeloid lineage cells in Cd11bCre;EP2(lox/lox) mice attenuated plasma inflammatory responses and transmission of systemic inflammation to the brain was inhibited, with decreased hippocampal inflammatory gene expression and cerebral cortical levels of IL-6. Conditional deletion of EP2 significantly blunted microglial and astrocytic inflammatory responses to the neurotoxin MPTP and reduced striatal dopamine turnover. Suppression of microglial EP2 signaling also increased numbers of dopaminergic (DA) neurons in the substantia nigra independent of MPTP treatment, suggesting that microglial EP2 may influence development or survival of DA neurons. Unbiased microarray analysis of microglia isolated from adult Cd11bCre;EP2(lox/lox) and control mice demonstrated a broad downregulation of inflammatory pathways with ablation of microglial EP2 receptor. Together, these data identify a cell-specific proinflammatory role for macrophage/microglial EP2 signaling in innate immune responses systemically and in brain.


Subject(s)
Brain/metabolism , Inflammation/metabolism , Macrophages/metabolism , Microglia/metabolism , Receptors, Prostaglandin E, EP2 Subtype/metabolism , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/pharmacology , Animals , Brain/drug effects , Dopaminergic Neurons/drug effects , Dopaminergic Neurons/metabolism , Inflammation/chemically induced , Inflammation/genetics , Lipopolysaccharides , Macrophages/drug effects , Mice , Mice, Transgenic , Microglia/drug effects , Receptors, Prostaglandin E, EP2 Subtype/genetics
9.
Eur J Trauma Emerg Surg ; 39(4): 415-9, 2013 Aug.
Article in English | MEDLINE | ID: mdl-26815403

ABSTRACT

Severe lower limb trauma with significant soft tissue injury can be managed with reconstruction or, if this is impossible, amputation. If amputation is considered, below-knee amputation preserving limb length is optimal for long-term functional outcome. At times, soft tissue/bony injury can limit the ability to preserve limb length, particularly with proximal tibial injuries. We present a case of elective below-knee amputation where leg length and adequate soft tissue coverage was only possible by using an osteocutaneous fillet of foot and lower leg spare parts free flap, maintaining the tibial nerve pedicle for sensation and the posterior tibial artery for vascularity of the nerve. The procedure was technically challenging and required follow-up debulking operations. However, the technique provided the significant advantage of immediate sensation of robust glabrous distal stump cover and optimising leg length to enhance functional outcome.

10.
J Psychopharmacol ; 26(11): 1443-55, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22219222

ABSTRACT

Previous findings indicate treatment with a selective serotonin reuptake inhibitor (SSRI) facilitates behavioral flexibility when conditions require inhibition of a learned response pattern. The present experiment investigated whether acute treatment with the SSRI, escitalopram, affects behavioral flexibility when conditions require inhibition of a naturally biased response pattern (elevated conflict test) and/or reversal of a learned response pattern (spatial reversal learning). An additional experiment was carried out to determine whether escitalopram, at doses that affected behavioral flexibility, also reduced anxiety as tested in the elevated plus-maze. In each experiment, Long-Evans rats received an intraperitoneal injection of either saline or escitalopram (0.03, 0.3 or 1.0 mg/kg) 30 min prior to behavioral testing. Escitalopram, at all doses tested, enhanced acquisition in the elevated conflict test, but did not affect performance in the elevated plus-maze. Escitalopram (0.3 and 1.0 mg/kg) did not alter acquisition of the spatial discrimination, but facilitated reversal learning. In the elevated conflict and spatial reversal learning test, escitalopram enhanced the ability to maintain the relevant strategy after being initially selected. The present findings suggest that enhancing serotonin transmission with an SSRI facilitates inhibitory processes when conditions require a shift away from either a naturally biased response pattern or a learned choice pattern.


Subject(s)
Citalopram/pharmacology , Maze Learning/drug effects , Reversal Learning/drug effects , Selective Serotonin Reuptake Inhibitors/pharmacology , Animals , Anxiety/drug therapy , Behavior, Animal/drug effects , Citalopram/administration & dosage , Disease Models, Animal , Dose-Response Relationship, Drug , Injections, Intraperitoneal , Male , Rats , Rats, Long-Evans , Serotonin/metabolism , Selective Serotonin Reuptake Inhibitors/administration & dosage
11.
Curr Oncol ; 19(6): e404-13, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23300364

ABSTRACT

BACKGROUND: Timeliness of care (rapid initiation of treatment after definitive diagnosis) is a key component of high-quality cancer treatment. The present study evaluated factors influencing timeliness of care for U.S. Medicare enrollees. METHODS: Data for Medicare enrollees diagnosed with breast, colorectal, lung, or prostate cancer while living in U.S. seer (Surveillance, Epidemiology and End Results) regions in 2000-2002 were analyzed. Patients were classified as experiencing delayed treatment if the interval between diagnosis and treatment was greater than the 95th percentile for each cancer site. The impacts of patient sociodemographic, clinical, and area-based factors on the likelihood of delayed treatment were analyzed using multivariate logistic regression. RESULTS: Black patients (compared with white patients) and patients initially treated with radiation therapy or chemotherapy (rather than surgery) had a greater likelihood of treatment delays across all four cancer sites. Hispanic status, dual Medicare-Medicaid status, location of initial treatment (inpatient vs. outpatient), and stage at diagnosis also affected timeliness of care for some cancer sites. Surprisingly, area-based factors reflecting availability of cancer care services were not significantly associated with timeliness of care or were associated with greater delays in areas with greater numbers of service providers. CONCLUSIONS: Multiple factors affected receipt of timely cancer care for members of the study population, all of whom had coverage of medical care services through Medicare. Because delays in treatment initiation can increase morbidity, decrease quality of life, shorten survival, and result in greater costs, prospective studies and tailored interventions are needed to address those factors among at-risk patient groups.

13.
Eur J Neurosci ; 34(12): 1997-2006, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22122410

ABSTRACT

Phasic changes in dopamine activity play a critical role in learning and goal-directed behavior. Unpredicted reward and reward-predictive cues evoke phasic increases in the firing rate of the majority of midbrain dopamine neurons--results that predict uniformly broadcast increases in dopamine concentration throughout the striatum. However, measurement of dopamine concentration changes during reward has cast doubt on this prediction. We systematically measured phasic changes in dopamine in four striatal subregions [nucleus accumbens shell and core (Core), dorsomedial (DMS) and dorsolateral striatum] in response to stimuli known to activate a majority of dopamine neurons. We used fast-scan cyclic voltammetry in awake and behaving rats, which measures changes in dopamine on a similar timescale to the electrophysiological recordings that established a relationship between phasic dopamine activity and reward. Unlike the responses of midbrain dopamine neurons, unpredicted food reward and reward-predictive cues evoked a phasic increase in dopamine that was subregion specific. In rats with limited experience, unpredicted food reward evoked an increase exclusively in the Core. In rats trained on a discriminative stimulus paradigm, both unpredicted reward and reward-predictive cues evoked robust phasic dopamine in the Core and DMS. Thus, phasic dopamine release in select target structures is dynamic and dependent on context and experience. Because the four subregions assayed receive different inputs and have differential projection targets, the regional selectivity of phasic changes in dopamine has important implications for information flow through the striatum and plasticity that underlies learning and goal-directed behavior.


Subject(s)
Corpus Striatum/anatomy & histology , Corpus Striatum/physiology , Dopamine/metabolism , Dopaminergic Neurons/physiology , Food , Reward , Signal Transduction/physiology , Action Potentials/physiology , Animals , Cues , Dopaminergic Neurons/cytology , Electric Stimulation , Learning/physiology , Male , Rats , Rats, Sprague-Dawley
14.
J Thorac Cardiovasc Surg ; 142(1): 203-8, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21130472

ABSTRACT

OBJECTIVE: Endoscopic vein harvesting systems have grown in popularity and are becoming the gold standard for coronary artery bypass grafting. Although a consensus is present that endoscopic vessel harvesting minimizes wound complications, long-term graft patency remains a concern. It has been proposed that endoscopic vessel harvesting affects graft patency because of irreversible trauma to the endothelium. This study was performed to examine the extent of thermal injury caused by 2 commercially available endoscopic vessel harvesting systems in a porcine model. METHODS: Superficial epigastric veins and saphenous arteries were exposed in 10 anesthetized swine. All vessel samples (conduits) were harvested randomly with either a VirtuoSaph (Terumo Cardiovascular, Ann Arbor, Mich) or VASOVIEW 6 (MAQUET, Inc, Wayne, NJ) endoscopic vessel harvesting system. Conduits were harvested and saved for either histologic analysis or burst-pressure test. Statistical differences were analyzed by using a Wilcoxon rank sum test in SAS 9.2 software (SAS Institute, Inc, Cary, NC) for thermal spread and a 2-tailed t test with equal variance for burst pressure. RESULTS: The average thermal spreads for saphenous artery and superficial epigastric vein conduits were significantly shorter in the VirtuoSaph group (0.42 ± 0.08 and 0.49 ± 0.05 mm, respectively) than in the VASOVIEW 6 group (1.05 ± .04 and 0.94 ± 0.19 mm, respectively). No significant differences were observed in burst pressure. CONCLUSIONS: The length of thermal spread is short in arterial and venous conduits (0.4-1.1 mm) and depends on the endoscopic vessel harvesting system. Clinical protocols should include a minimal length of the cauterized branch to ensure that thermal spread does not reach the main vessel. The results of this study suggest that at least 1 mm is sufficient.


Subject(s)
Abdominal Muscles/blood supply , Electrocoagulation/instrumentation , Endoscopy/instrumentation , Lower Extremity/blood supply , Tissue and Organ Harvesting/instrumentation , Animals , Arteries/injuries , Arteries/transplantation , Electrocoagulation/adverse effects , Endoscopy/adverse effects , Equipment Design , Graft Occlusion, Vascular/etiology , Graft Occlusion, Vascular/pathology , Materials Testing , Models, Animal , Pressure , Swine , Vascular Patency , Vascular System Injuries/etiology , Vascular System Injuries/pathology , Veins/injuries , Veins/transplantation
15.
J Neurosci ; 30(43): 14390-8, 2010 Oct 27.
Article in English | MEDLINE | ID: mdl-20980596

ABSTRACT

Recent evidence suggests that a circuit involving the centromedian-parafascicular (Pf) thalamus and basal ganglia is critical for a shift away from biased actions. In particular, excitatory input from the Pf onto striatal cholinergic neurons may facilitate behavioral flexibility. Accumulating evidence indicates that an endogenous increase in dorsomedial striatal acetylcholine (ACh) output enhances behavioral flexibility. The present experiments investigated whether the rat (Rattus norvegicus) Pf supports flexibility during reversal learning, in part, by modifying dorsomedial striatal ACh output. This was determined first by examining the effects of Pf inactivation, through infusion of the GABA agonists baclofen and muscimol, on place acquisition and reversal learning. Additional experiments examined Pf inactivation on dorsomedial striatal ACh output during reversal learning and a resting condition. Behavioral testing was performed in a cross-maze. In vivo microdialysis combined with HPLC/electrochemical detection was used to sample ACh from the dorsomedial striatum. Pf inactivation selectively impaired reversal learning in a dose-dependent manner. A subsequent study showed that an increase in dorsomedial striatal ACh efflux (∼30% above basal levels) during reversal learning was blocked by Pf inactivation, which concomitantly impaired reversal learning. In the resting condition, a dose of baclofen and muscimol that blocked a behaviorally induced increase in dorsomedial striatal ACh output did not reduce basal ACh efflux. Together, the present findings indicate that the Pf is an intralaminar thalamic nucleus critical for behavioral flexibility, in part, by directly affecting striatal ACh output under conditions that require a shift in choice patterns.


Subject(s)
Acetylcholine/metabolism , Behavior, Animal/physiology , Corpus Striatum/metabolism , Intralaminar Thalamic Nuclei/physiology , Animals , Baclofen/pharmacology , Chromatography, High Pressure Liquid , Discrimination, Psychological/physiology , GABA Agonists/pharmacology , Learning/physiology , Male , Microdialysis , Muscimol/pharmacology , Rats , Rats, Long-Evans , Reversal Learning/physiology
16.
Mol Microbiol ; 66(2): 329-40, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17850254

ABSTRACT

Adherence to host cells is important in microbial colonization of a mucosal surface, and Streptococcus pneumoniae adherence was significantly enhanced by expression of an extracellular pilus composed of three subunits, RrgA, RrgB and RrgC. We sought to determine which subunit(s) confers adherence. Bacteria deficient in RrgA are significantly less adherent than wild-type organisms, while overexpression of RrgA enhances adherence. Recombinant monomeric RrgA binds to respiratory cells, as does RrgC with less affinity, and pre-incubation of epithelial cells with RrgA reduces adherence of wild-type piliated pneumococci. Non-adherent RrgA-negative, RrgB- and RrgC-positive organisms produce pili, suggesting that pilus-mediated adherence is due to expression of RrgA, rather than the pilus backbone itself. In contrast, RrgA-positive strains with disrupted rrgB and rrgC genes exhibit wild-type adherence despite failure to produce pili by Western blot or immunoelectron microscopy. The density of bacteria colonizing the upper respiratory tract of mice inoculated with piliated RrgA-negative pneumococci was significantly less compared with wild-type; in contrast, non-piliated pneumococci expressing non-polymeric RrgA had similar numbers of bacteria in the nasopharynx as piliated wild-type bacteria. These data suggest that RrgA is central in pilus-mediated adherence and disease, even in the absence of polymeric pilus production.


Subject(s)
Adhesins, Bacterial/physiology , Bacterial Adhesion/physiology , Fimbriae Proteins/physiology , Streptococcus pneumoniae/metabolism , Adhesins, Bacterial/genetics , Adhesins, Bacterial/metabolism , Animals , Bacterial Adhesion/genetics , Blotting, Western , Cell Line, Tumor , Epithelial Cells/microbiology , Fimbriae Proteins/genetics , Fimbriae Proteins/metabolism , Gene Expression Regulation, Bacterial , Humans , Mice , Mice, Inbred C57BL , Microscopy, Immunoelectron , Protein Binding , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Streptococcus pneumoniae/genetics , Streptococcus pneumoniae/ultrastructure
17.
Emerg Med J ; 23(12): 948-52, 2006 Dec.
Article in English | MEDLINE | ID: mdl-17130609

ABSTRACT

AIMS: To determine ambulance transport rates and investigate predictors for ambulance use by patients with acute myocardial infarction (AMI) in Australia. METHODS: A prospective, cross-sectional descriptive survey using structured interviews. It included patients who were admitted to two hospitals (Western, Bendigo, Melbourne, Victoria, Australia) with AMI between 1 October 2004 and 31 March 2005, and data were collected by semistructured interview and medical record review. Data were analysed by descriptive statistics, univariate and multivariate analysis using SPSS. RESULTS: 105 patients were interviewed. 48 (46%) participants called for an ambulance as their initial medical contact. Participants who called for an ambulance had a shorter interval between symptom onset and presentation to hospital than those who did not (non-ambulance participants)(median 2.1 v 7.8 h; p = 0.001). Predictors of ambulance transport were older age (p = 0.008), symptom onset on the weekend (p = 0.022), presence of sharp chest pain (p = 0.011), self-administered anginine (p = 0.007), symptom onset at home (p = 0.027) and having a lower income (

Subject(s)
Ambulances/statistics & numerical data , Myocardial Infarction/therapy , Patient Acceptance of Health Care/statistics & numerical data , Adult , Age Factors , Aged , Aged, 80 and over , Australia , Epidemiologic Methods , Female , Humans , Male , Middle Aged , Myocardial Infarction/psychology , Nitroglycerin/administration & dosage , Self Administration , Time Factors , Vasodilator Agents/administration & dosage
18.
J Small Anim Pract ; 47(6): 325-35, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16761985

ABSTRACT

OBJECTIVES: To evaluate the clinical, clinical pathology, diagnostic imaging, microbiological and pathological features of cholangitis/cholangiohepatitis in the dog. METHODS: The study design was a retrospective review of cases of bacterial cholangitis/cholangiohepatitis presented to the University of Bristol during the period 1995 to 2000. The diagnosis was made based on hepatic histopathological findings and positive bile culture results. RESULTS: Four dogs met the inclusion criteria. Common presenting signs included anorexia (n=4), jaundice (n=4), vomiting (n=4) and pyrexia (n=2). All four dogs had a leucocytosis or neutrophilia reported at some time in their history along with serum bilirubin elevation. In addition, serum alkaline phosphatase and alanine transaminase activity was increased in all of the dogs in which it was measured both before and at the time of referral. In general, the diagnostic imaging findings were non-specific. Organisms cultured from bile aspirates were Escherichia coli (n=3), Clostridium species (n=2) and a faecal Streptococcus species (n=1). Two cases resolved with medical treatment alone; two with concurrent cholecystitis required cholecystectomy. Following surgery, both of these cases showed a resolution of clinical signs. CLINICAL SIGNIFICANCE: This report highlights the fact that bacterial cholangitis/cholangiohepatitis with or without concurrent cholecystitis should be considered as a potential differential in dogs presenting with signs referable to biliary tract disease.


Subject(s)
Bacterial Infections/veterinary , Cholangitis/veterinary , Cholecystitis/veterinary , Dog Diseases/epidemiology , Alkaline Phosphatase/blood , Animals , Anti-Bacterial Agents/administration & dosage , Bacterial Infections/complications , Bacterial Infections/epidemiology , Bile/microbiology , Bilirubin/blood , Blood Chemical Analysis/veterinary , Cholangitis/complications , Cholangitis/epidemiology , Cholecystectomy/veterinary , Cholecystitis/complications , Cholecystitis/epidemiology , Dog Diseases/blood , Dog Diseases/diagnosis , Dog Diseases/diagnostic imaging , Dog Diseases/microbiology , Dog Diseases/pathology , Dog Diseases/therapy , Dogs , Female , Ireland/epidemiology , Male , Medical Records , Retrospective Studies , Ultrasonography
19.
Proc Natl Acad Sci U S A ; 103(8): 2857-62, 2006 Feb 21.
Article in English | MEDLINE | ID: mdl-16481624

ABSTRACT

Streptococcus pneumoniae (pneumococcus) is a major cause of morbidity and mortality world-wide. The initial event in invasive pneumococcal disease is the attachment of encapsulated pneumococci to epithelial cells in the upper respiratory tract. This work provides evidence that initial bacterial adhesion and subsequent ability to cause invasive disease is enhanced by pili, long organelles able to extend beyond the polysaccharide capsule, previously unknown to exist in pneumococci. These adhesive pili-like appendages are encoded by the pneumococcal rlrA islet, present in some, but not all, clinical isolates. Introduction of the rlrA islet into an encapsulated rlrA-negative isolate allowed pilus expression, enhanced adherence to lung epithelial cells, and provided a competitive advantage upon mixed intranasal challenge of mice. Furthermore, a pilus-expressing rlrA islet-positive clinical isolate was more virulent than a nonpiliated deletion mutant, and it out-competed the mutant in murine models of colonization, pneumonia, and bacteremia. Additionally, piliated pneumococci evoked a higher TNF response during systemic infection, compared with nonpiliated derivatives, suggesting that pneumococcal pili not only contribute to adherence and virulence but also stimulate the host inflammatory response.


Subject(s)
Fimbriae, Bacterial/physiology , Genes, Bacterial/physiology , Genomic Islands , Pneumonia, Bacterial/microbiology , Streptococcus pneumoniae/genetics , Streptococcus pneumoniae/pathogenicity , Animals , Bacterial Adhesion/genetics , Bacterial Proteins/genetics , Fimbriae, Bacterial/genetics , Fimbriae, Bacterial/ultrastructure , Genes, Bacterial/genetics , Genomic Islands/genetics , Genomic Islands/physiology , Mice , Mice, Inbred C57BL , Mutation , Respiratory Mucosa/microbiology , Streptococcus pneumoniae/ultrastructure , Trans-Activators/genetics , Virulence
20.
Ultrasound Obstet Gynecol ; 23(1): 23-9, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14970994

ABSTRACT

OBJECTIVE: Female fetuses, on average, weigh less than male fetuses at all gestational ages. The purpose of this study was to compare female and male fetuses in terms of intrauterine ultrasound growth measurements and to develop gestational-age-related charts based on a computerized perinatal database. METHODS: This was a retrospective study of unselected women in the second and third trimesters of pregnancy, who had a normal scan at 10-14 weeks. Data analysis was performed using measurements obtained from a mixed-race population of 4234 women, who underwent 5198 ultrasound examinations. The scans were performed by four trained sonographers, according to a standardized protocol. Routine measurements included biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC) and femur length (FL). The main end-points were sex- and race-specific differences in fetal biometry, which were also used to estimate fetal weight. RESULTS: The base-line demographic characteristics and risk factors were comparable in female and male fetuses. Significant differences in fetal BPD, HC, AC and estimated fetal weight, but not FL, were seen between male and female fetuses. Centile charts for each of these variables were constructed for both male and female fetuses. CONCLUSIONS: This study suggests that small but consistent sex-related differences in prenatal BPD, HC and AC measurements are established by as early as 15 weeks of gestation. The use of sex-specific nomograms may improve the prenatal assessment of fetal growth as well as the diagnosis of structural abnormalities.


Subject(s)
Embryonic and Fetal Development/physiology , Sex Characteristics , Ultrasonography, Prenatal , Female , Gestational Age , Head/embryology , Humans , Male , Pregnancy , Pregnancy Trimester, Second , Pregnancy Trimester, Third , Reference Standards , Retrospective Studies
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