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1.
J Antimicrob Chemother ; 74(8): 2119-2121, 2019 08 01.
Article in English | MEDLINE | ID: mdl-30989175

ABSTRACT

Bone and joint infection contributes significantly to clinical activity within outpatient parenteral antimicrobial therapy (OPAT) services. The OVIVA (oral versus intravenous antibiotics for bone and joint infection) randomized study has challenged the practice of prolonged intravenous therapy, because non-inferiority of oral antibiotic therapy was demonstrated, thereby implying that early transition to oral therapy is an appropriate alternative to prolonged intravenous therapy. We examine the caveats to the study and discuss the implications for OPAT practice, highlighting the importance of careful oral antibiotic selection with attention to bioavailability, bone penetration, drug interactions, compliance and toxicity monitoring. We emphasize that ambulatory antibiotic therapy (whether intravenous or oral) in this patient group requires expert multidisciplinary management, monitoring and follow-up, and ideally should be undertaken within existing OPAT or, more accurately, complex outpatient antibiotic therapy (COpAT) services.


Subject(s)
Ambulatory Care , Anti-Bacterial Agents/therapeutic use , Bone Diseases, Infectious/drug therapy , Disease Management , Administration, Oral , Ambulatory Care Facilities , Arthritis, Infectious/drug therapy , Humans , Infusions, Parenteral , Joints/microbiology , Multicenter Studies as Topic , Randomized Controlled Trials as Topic
3.
Transfus Med ; 23(4): 250-3, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23617356

ABSTRACT

BACKGROUND: Alloantibodies against human platelet antigens (HPAs) are responsible for the development of alloimmune thrombocytopenia including platelet transfusion refractoriness (PTR) and neonatal alloimmune thrombocytopenia (NAIT). Therefore, transfusion of HPA-compatible platelets is of importance for the management of these diseases. AIM: Determination of the allele frequency of the major HPA systems for Indonesian blood donors and the development of the first HPA-typed donor registry in Indonesia. METHODS: DNA derived from 500 Indonesian healthy blood donors was genotyped for HPA-1 to HPA-6 and HPA-15 alleles by the use of polymerase chain reaction sequence-specific primer method. RESULTS: The gene frequencies of the rare allelic variants HPA-1b, -2b, -3b, -4b, -5b, -6b and -15b were 0·023, 0·060, 0·493, 0·052, 0·032, 0·044 and 0·049, respectively. However, donors homozygous for the HPA-1b, -2b and -6b were not found in this cohort, indicating that the risks of alloimmunisation caused by incompatibility of these three HPA systems are extremely low. In contrast, alloimmunisation against HPA-3, -4, -5 and -15 systems is anticipated. CONCLUSION: The development of an HPA-genotyped registry for donors homozygous for HPA-1b, -2b and -6b is desired for the optimum management of PTR patients and children with NAIT.


Subject(s)
Antigens, Human Platelet/genetics , Blood Donors , Gene Frequency/genetics , Antigens, Human Platelet/metabolism , Blood Group Incompatibility/blood , Blood Group Incompatibility/genetics , Blood Platelets/metabolism , Female , Humans , Indonesia , Male , Platelet Transfusion/adverse effects , Platelet Transfusion/methods , Thrombocytopenia, Neonatal Alloimmune/blood , Thrombocytopenia, Neonatal Alloimmune/etiology , Thrombocytopenia, Neonatal Alloimmune/genetics
4.
J Microsc ; 233(2): 331-9, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19220700

ABSTRACT

In this paper, we present Monte Carlo simulation results demonstrating the feasibility of using the focused ion beam based X-ray microanalysis technique (FIB-EDS) for the 3D elemental analysis of biological samples. In this study, we used a marine diatom Thalassiosira pseudonana as our model organism and NISTMonte for the Monte Carlo simulations. We explored several beam energies commonly used for the X-ray microanalysis to examine their effects on the resulting 3D elemental volume of the model organism. We also performed a preliminary study on the sensitivity of X-ray analysis for detecting nanoparticles in the model. For the conditions considered in this work, we show that the X-ray mapping performed using the 5 keV beam energy results in 3D elemental distributions that closely reflect the elemental distributions in the original model. At 5 keV, the depth resolution of the X-ray maps is about 250 nm for the model organism. We also show that the nanoparticles that are 50 nm in diameter or greater are easily located. Although much work is still needed in generating more accurate biological models and simulating experimental conditions relevant to these samples, our results indicate that FIB-EDS is a promising technique for the 3D elemental analysis of some biological specimens.


Subject(s)
Artifacts , Diatoms/ultrastructure , Electron Probe Microanalysis/methods , Imaging, Three-Dimensional/methods , Monte Carlo Method , Nanoparticles/ultrastructure
5.
Article in English | MEDLINE | ID: mdl-33061254

ABSTRACT

Differential thermal analysis (DTA) and microstructural and microprobe measurements of DTA and as-cast Ni-Re alloys with compositions between 0.20 and 0.44 mass fraction Re provide information to resolve differences in previously published Ni-Re phase diagrams. This investigation determines that the peritectic invariant between liquid, Re-rich hexagonal close packed and Ni-rich face center cubic phases, L + HCP → FCC, occurs at 1561.1 °C ± 3.4 °C (1σ) with compositions of liquid, FCC and HCP phases of 0.283 ± 0.036, 0.436 ± 0.026, and 0.828 ± 0.037 mass fraction Re, respectively. Analysis of the microsegregation in FCC alloys yields a partition coefficient for solidification, k = 1.54 ± 0.09 (mass frac./mass frac.). A small deviation from Scheil behavior due to dendrite tip kinetics is documented in as-cast samples. No evidence of an intermetallic phase is observed.

6.
J Neural Eng ; 4(2): 35-41, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17409478

ABSTRACT

The interaction of murine embryonic cortical neurons on randomly orientated electrospun scaffolds of poly(L-lactide) (P(L)LA) and poly(lactide-co-glycolide) (PLGA) is investigated in this study. The scaffolds were surface treated with different concentrations of KOH to partially hydrolyze the surface and therefore change the surface tension. Hydrophilicity did not significantly influence the number of primary and secondary branches; however, it had a considerable effect on neurite extension. For scaffolds with surface tensions of 40-47 dyn cm(-1) there was a significantly greater overall neurite length for both the primary and secondary branches compared with more hydrophilic scaffolds. Another major finding of this work was that the interfibre distance influenced how the neurites extended. When the interfibre distance was greater than approximately 15 microm the neurites followed the fibres and avoided regions of very high fibre density. At interfibre distances less than approximately 15 microm, the neurites traversed between the fibres. Therefore, this study provided little evidence that contact guidance was the dominating cue in directing neurite extension, instead inferring that chemical cues, possibly from adjacent neurons had induced directional change.


Subject(s)
Cerebral Cortex/embryology , Guided Tissue Regeneration/methods , Lactic Acid/chemistry , Nanostructures/chemistry , Neurons/cytology , Neurons/physiology , Polyglycolic Acid/chemistry , Polymers/chemistry , Tissue Engineering/methods , Animals , Biocompatible Materials/chemistry , Cell Culture Techniques/methods , Cell Enlargement , Cells, Cultured , Cerebral Cortex/cytology , Cerebral Cortex/physiology , Guided Tissue Regeneration/instrumentation , Mice , Mice, Inbred C57BL , Nanostructures/ultrastructure , Particle Size , Polylactic Acid-Polyglycolic Acid Copolymer , Surface Properties
7.
QJM ; 110(3): 155-161, 2017 Mar 01.
Article in English | MEDLINE | ID: mdl-27521583

ABSTRACT

INTRODUCTION: : Antimicrobial stewardship has an important role in the control of Clostridium difficile infection (CDI) and antibiotic resistance. An important component of UK stewardship interventions is the restriction of broad-spectrum beta-lactam antibiotics and promotion of agents associated with a lower risk of CDI such as gentamicin. While the introduction of restrictive antibiotic guidance has been associated with improvements in CDI and antimicrobial resistance, evidence of the effect on outcome following severe infection is lacking. METHODS: : In 2008, Glasgow hospitals introduced a restrictive antibiotic guideline. A retrospective before/after study assessed outcome following Gram-negative bacteraemia in the 2-year period around implementation. RESULTS: : Introduction of restrictive antibiotic guidelines was associated with a reduction in utilization of ceftriaxone and co-amoxiclav and an increase in amoxicillin and gentamicin. Approximately 1593 episodes of bacteremia were included in the study. The mortality over 1-year following Gram-negative bacteraemia was lower in the period following guideline implementation (RR 0.852, P = 0.045). There was no evidence of a difference in secondary outcomes including ITU admission, length of stay, readmission, recurrence of bacteraemia and need for renal replacement therapy. There was a fall in CDI (RR 0.571, P = 0.014) and a reduction in bacterial resistance to ceftriaxone and co-amoxiclav but no evidence of an increase in gentamicin resistance after guideline implementation. CONCLUSION: : Restrictive antibiotic guidelines were associated with a reduction in CDI and bacterial resistance but no evidence of adverse outcomes following Gram-negative bacteraemia. There was a small reduction in one year mortality.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Gram-Negative Bacterial Infections/drug therapy , Aged , Bacteremia/drug therapy , Bacteremia/mortality , Clostridioides difficile , Clostridium Infections/drug therapy , Clostridium Infections/epidemiology , Drug Resistance, Bacterial , Drug Utilization/statistics & numerical data , Female , Gram-Negative Bacterial Infections/mortality , Hospital Mortality , Humans , Length of Stay/statistics & numerical data , Male , Middle Aged , Practice Guidelines as Topic , Practice Patterns, Physicians'/statistics & numerical data , Retrospective Studies , Scotland/epidemiology , Systemic Inflammatory Response Syndrome/drug therapy , Systemic Inflammatory Response Syndrome/mortality
8.
Int J Tuberc Lung Dis ; 21(6): 677-683, 2017 06 01.
Article in English | MEDLINE | ID: mdl-28482963

ABSTRACT

SETTING: Glasgow, Scotland, UK. BACKGROUND: Paradoxical reactions in tuberculosis (TB) are a notable example of our incomplete understanding of host-pathogen interactions during anti-tuberculosis treatment. OBJECTIVES: To determine risk factors for a TB paradoxical reaction, and specifically to assess for an independent association with vitamin D use. DESIGN: Consecutive human immunodeficiency virus (HIV) negative adult patients treated for extra-pulmonary TB were identified from an Extended Surveillance of Mycobacterial Infections database. In our setting, vitamin D was variably prescribed for newly diagnosed TB patients. A previously published definition of paradoxical TB reaction was retrospectively applied to, and data on all previously described risk factors were extracted from, centralised electronic patient records. The association with vitamin D use was assessed using multivariate logistic regression. RESULTS: Of the 249 patients included, most had TB adenopathy; 222/249 had microbiologically and/or histologically confirmed TB. Vitamin D was prescribed for 57/249 (23%) patients; 37/249 (15%) were classified as having paradoxical reactions. Younger age, acid-fast bacilli-positive invasive samples, multiple disease sites, lower lymphocyte count and vitamin D use were found to be independent risk factors. CONCLUSION: We speculate that vitamin D-mediated signalling of pro-inflammatory innate immune cells, along with high antigenic load, may mediate paradoxical reactions in anti-tuberculosis treatment.


Subject(s)
Antitubercular Agents/therapeutic use , Tuberculosis, Lymph Node/drug therapy , Tuberculosis/drug therapy , Vitamin D/administration & dosage , Adult , Age Factors , Cohort Studies , Female , Host-Pathogen Interactions , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , Retrospective Studies , Risk Factors , Scotland , Treatment Outcome , Tuberculosis/microbiology , Tuberculosis, Lymph Node/microbiology
9.
Sci Rep ; 6: 35838, 2016 11 02.
Article in English | MEDLINE | ID: mdl-27804985

ABSTRACT

Pseudomonas aeruginosa (PA) remains an important pathogen in patients with cystic fibrosis (CF) lung disease as well as non-CF bronchiectasis and chronic obstructive airways disease. Initial infections are cleared but chronic infection with mucoid strains ensues in the majority of CF patients and specific interventions to prevent this critical infection transition are lacking. The PA bead model has been widely used to study pulmonary P.aeruginosa infection but has limitations in animal husbandry and in accurately mimicking human disease. We have developed an adapted agar bead murine model using a clinical mucoid strain that demonstrates the key features of transition from transitory to chronic airways infection. Infected animals show very limited acute morbidity and mortality, but undergo infection-related weight loss and neutrophilic inflammation, development of anti-pseudomonal antibodies, variable bacterial clearance, endobronchial infection and microbial adaptation with PA small colony variants. We anticipate this model will allow research into the host and microbial factors governing this critical period in Pseudomonas aeruginosa pulmonary pathogenesis when transition to chronicity is occurring.


Subject(s)
Pseudomonas Infections/pathology , Pseudomonas aeruginosa/pathogenicity , Respiratory Tract Infections/pathology , Animals , Antibodies, Bacterial/blood , B-Lymphocytes/cytology , Bronchoalveolar Lavage Fluid/cytology , Chronic Disease , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Immunoglobulin G/blood , Inflammation/pathology , Lung/immunology , Lung/pathology , Lymph Nodes/cytology , Mice , Mice, Inbred C57BL , Neutrophils/cytology , Neutrophils/immunology , Pseudomonas Infections/microbiology , Pseudomonas aeruginosa/immunology , Respiratory Tract Infections/microbiology
11.
Vet J ; 153(2): 221-4, 1997 Mar.
Article in English | MEDLINE | ID: mdl-12463408

ABSTRACT

Cylindrical rumen boluses of a size (55 mm length x 18 mm diameter, density 2.9 g cm(-3)) appropriate for ruminating calves over 75 kg liveweight were constructed. The mean daily nutrient releases from two rumen boluses measured in rumen-cannulated cows were 62 mg Cu, 0.56 mg Se, 1.08 mg Co, 1.14 mg I, 38 mg Mn and 55 mg Zn with vitamins 3140 IU A, 628 IU D3 and 9 IU E. In a 123-day experiment with housed dairy calves given hay and a barley/soyabean meal mix, administration of two rumen boluses significantly increased plasma copper and blood glutathione peroxidase levels compared with unsupplemented control calves. There were similarly significant responses in a 143-day experiment with suckled beef-cross calves treated with two rumen boluses at grass. In both circumstances the basic diets provided inadequate allowances of both copper and selenium.


Subject(s)
Cattle/physiology , Glutathione Peroxidase/pharmacology , Nutritional Support , Trace Elements/administration & dosage , Animals , Animals, Newborn , Copper/administration & dosage , Copper/blood , Copper/pharmacology , Delayed-Action Preparations , Glutathione Peroxidase/analysis , Nutritional Status , Nutritional Support/veterinary , Rumen , Trace Elements/pharmacology
12.
Med Dosim ; 28(3): 185-8, 2003.
Article in English | MEDLINE | ID: mdl-14563438

ABSTRACT

Palladium-103-(103Pd) seed has been increasingly used in prostate implantation as either definitive or boost therapy because of its shorter half-life and higher initial dose rate. Because a growing number of radiation oncologists prefer real-time implantation in the operating room, it will be helpful if the total activity of the seeds can be determined based on the gland size before the patient is taken to the operating room. Based on our clinic data, nomograms have therefore been developed for one of the widely used 103Pd seeds, the MED3633 seed, which is produced by North American Scientific, Inc. (NASI). The total activities for implant volume ranging from 15 cc to 55 cc are provided for both seed "monotherapy" and seed boost.


Subject(s)
Brachytherapy/instrumentation , Palladium , Prostatic Neoplasms/radiotherapy , Humans , Male , Palladium/therapeutic use , Radioisotopes/therapeutic use
13.
Small Rumin Res ; 39(1): 25-30, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11163712

ABSTRACT

A sustained-release multi-trace element/vitamin bolus has been devised for administration to ewes in advance of mating. Each bolus contained 5.3g Cu, 50mg Se, 90mg Co, 100mg I, 3.2g Mn and 4.7g Zn with 268x10(3) IU Vitamin A, 54x10(3) IU Vitamin D and 800 IU Vitamin E. About 50% of each nutrient is released during the first 6 weeks. Thereafter the release rate slows and over the remaining life of the bolus (about 6 months extending to lambing time) the daily release rates are about 15mg Cu, 0.1mg Se, 0.2mg Co, 0.3mg I, 9.4mg Mn and 13mg Zn with 775 IU Vitamin A, 156 IU Vitamin D and 2 IU Vitamin E. In one study the proportion of twins born to ewes given the bolus was very significantly (P<0.001) higher than for the untreated ewes and greater than for those given a copper injection or copper oxide needles. In a second study the proportion of ewes given a bolus and having twin lambs was significantly (P<0.01) greater than for untreated ewes and significantly (P<0.05) fewer ewes were non-pregnant. In a third study, giving a bolus to shearling ewes tended (P=0.06) to result in fewer non-pregnant animals than for those untreated. Blood copper and Vitamin B(12) concentrations and glutathione peroxidase activities were above normal values throughout.

14.
QJM ; 107(3): 207-11, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24300160

ABSTRACT

BACKGROUND: It is recommended that venous thromboembolism (VTE) prophylaxis be considered for patients receiving outpatient parenteral antimicrobial therapy (OPAT), but there is no published data to quantify VTE risk in this patient group. AIM AND METHOD: The aim of this retrospective cohort study was to establish VTE incidence in patients managed through an OPAT service and assess utility of a common VTE prediction score normally used for inpatients. Consecutive episodes of OPAT between May 2009 and May 2012 were included. Patients on long-term anti-coagulants, those with an established indication for extended, outpatient VTE prophylaxis (i.e. patients referred to OPAT following hip or knee arthroplasty) were excluded. The Padua VTE Prediction Score was retrospectively applied to the cohort. The primary outcome was incidence of symptomatic VTE during or up to 90 days after completion of OPAT treatment. RESULTS: There were 780 included patient episodes; 105 (13.5%) patients had a Padua VTE risk score >3; no patients received pharmacological VTE prophylaxis during OPAT treatment. During or up to 90 days following OPAT, two proximal lower limb DVTs were diagnosed, giving VTE incidence of 2/780 (0.26%, 95% CI: 0.03-0.92%), and there were eight deaths of which none were suspected to be related to VTE. There was one intracranial haemorrhage associated death. CONCLUSION: This retrospective cohort study found a low incidence of VTE in OPAT patients, and does not support routine application of inpatient VTE prophylaxis algorithms to patients treated for infection in the community.


Subject(s)
Anti-Infective Agents/adverse effects , Bacterial Infections/drug therapy , Venous Thromboembolism/chemically induced , Adult , Ambulatory Care/statistics & numerical data , Anti-Infective Agents/administration & dosage , Community-Acquired Infections/drug therapy , Female , Humans , Infusions, Parenteral , Kaplan-Meier Estimate , Male , Middle Aged , Retrospective Studies , Risk Factors
19.
Appl Environ Microbiol ; 65(4): 1378-83, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10103225

ABSTRACT

Little is known about Ceanothus-infective Frankia strains because no Frankia strains that can reinfect the host plants have been isolated from Ceonothus spp. Therefore, we studied the diversity of the Ceonothus-infective Frankia strains by using molecular techniques. Frankia strains inhabiting root nodules of nine Ceanothus species were characterized. The Ceanothus species used represent the taxonomic diversity and geographic range of the genus; therefore, the breadth of the diversity of Frankia strains that infect Ceanothus spp. was studied. DNA was amplified directly from nodular material by using the PCR. The amplified region included the 3' end of the 16S rRNA gene, the intergenic spacer, and a large portion of the 23S rRNA gene. A series of restriction enzyme digestions of the PCR product allowed us to identify PCR-restriction fragment length polymorphism (RFLP) groups among the Ceanothus-infective Frankia strains tested. Twelve different enzymes were used, which resulted in four different PCR-RFLP groups. The groups did not follow the taxonomic lines of the Ceanothus host species. Instead, the Frankia strains present were related to the sample collection locales.


Subject(s)
Actinomycetales/classification , Actinomycetales/genetics , Genetic Variation , Plants/microbiology , DNA, Bacterial/genetics , Genes, rRNA , Molecular Sequence Data , Polymerase Chain Reaction/methods , Polymorphism, Restriction Fragment Length , RNA, Ribosomal, 16S/genetics , RNA, Ribosomal, 23S/genetics , Sequence Analysis, DNA , United States
20.
Mol Phylogenet Evol ; 13(3): 493-503, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10620407

ABSTRACT

Molecular phylogenetic trees were reconstructed from nucleotide sequences of nifH and 16S rDNA for Frankia and of rbcL for actinorhizal plants. Comparison of Frankia phylogenetic trees reconstructed using nifH and 16S rDNA sequences indicated that subgroupings of both trees correspond with each other in terms of plant origins of Frankia strains. The results suggested that 16S rDNAs can be utilized for coevolution analysis of actinorhizal symbioses. Frankia and plant phylogenetic trees reconstructed using 16S rDNA and rbcL sequences were compared. The comparison by tree matching and likelihood ratio tests indicated that although branching orders of both trees do not strictly correspond with each other, subgroupings of Frankia and their host plants correspond with each other in terms of symbiotic partnership. Estimated divergence times among Frankia and plant clades indicated that Frankia clades diverged more recently than plant clades. Taken together, actinorhizal symbioses originated more than three times after the four plant clades diverged.


Subject(s)
Actinomycetales/physiology , Evolution, Molecular , Oxidoreductases , Phylogeny , Plants/microbiology , Ribulose-Bisphosphate Carboxylase , Symbiosis/physiology , Actinomycetales/genetics , Chromosomes, Fungal/genetics , DNA, Ribosomal/genetics , Fungal Proteins/genetics , Nitrogenase/genetics , Plant Physiological Phenomena , Plant Proteins/genetics , Time Factors
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