1,337 research outputs found
Death following bilateral complete Achilles tendon rupture in a patient on fluoroquinolone therapy: a case report
<p>Abstract</p> <p>Introduction</p> <p>Risk of tendon rupture, especially of the Achilles tendon, is one of the many potential side-effects of fluoroquinolone therapy. Achilles tendon rupture may be painful, debilitating or, as seen in our patient, devastating. While fluoroquinolone-induced tendon rupture typically accompanies other comorbidities (for example renal impairment) or concurrent steroid therapy, our case represents a medical 'first' in that there were no such comorbidities and no steroid therapy. Furthermore, our case is remarkable in that tendon rupture was bilateral, complete, and resulted in a devastating outcome.</p> <p>Case presentation</p> <p>A healthy 91-year-old Caucasian man was placed on fluoroquinolone (levofloxacin) therapy for a presumed bacterial pneumonitis. Subsequently, he developed bilateral heel pain, edema, and ecchymoses leading to a diagnosis of bilateral complete Achilles tendon rupture. This drug's side-effect was directly responsible for his subsequent physical and psychologic decline and unfortunate death.</p> <p>Conclusion</p> <p>Fluoroquinolones are a powerful and potent tool in the fight against bacterial infection. As a class, they are employed by primary care physicians as well as by subspecialty physicians in all areas of medical practice. However, as this case illustrates, the use of these drugs is not without risk. Attention must be paid to potential side-effects when prescribing any medication, and close follow-up with patients is a medical necessity to evaluate for these adverse reactions, especially with fluoroquinolones.</p
Truncation of the lipopolysaccharide outer core affects susceptibility to antimicrobial peptides and virulence of Actinobacillus pleuropneumoniae serotype 1.
Abstract We reported previously that the core oligosaccharide region of the lipopolysaccharide (LPS) is essential for optimal adhesion of Actinobacillus pleuropneumoniae, an important swine pathogen, to respiratory tract cells. Rough LPS and core LPS mutants of A. pleuropneumoniae serotype 1 were generated by using a mini-Tn10 transposon mutagenesis system. Here we performed a structural analysis of the oligosaccharide region of three core LPS mutants that still produce the same O-antigen by using methylation analyses and mass spectrometry. We also performed a kinetic study of proinflammatory cytokines production such as interleukin (IL)-6, tumor necrosis factor-α, IL1-β, MCP-1, and IL8 by LPS-stimulated porcine alveolar macrophages, which showed that purified LPS of the parent strain, the rough LPS and core LPS mutants, had the same ability to stimulate the production of cytokines. Most interestingly, an in vitro susceptibility test of these LPS mutants to antimicrobial peptides showed that the three core LPS mutants were more susceptible to cationic peptides than both the rough LPS mutant and the wild type parent strain. Furthermore, experimental pig infections with these mutants revealed that the galactose (Gal I) and d,d-heptose (Hep IV) residues present in the outer core of A. pleuropneumoniae serotype 1 LPS are important for adhesion and overall virulence in the natural host, whereas deletion of the terminal GalNAc-Gal II disaccharide had no effect. Our data suggest that an intact core-lipid A region is required for optimal protection of A. pleuropneumoniae against cationic peptides and that deletion of specific residues in the outer LPS core results in the attenuation of the virulence of A. pleuropneumoniae serotype 1
The Changing Nature of Poverty
Since the beginning of the War on Poverty, the poverty rate has fluctuated widely, and at the same time the poverty population has undergone many changes, some mirroring the changing stereotypes of the poor and others less pronounced than the changing stereotypes would lead us to believe. A feminization of poverty has occurred, with many more of the poor now in households headed by women. Interestingly, aging of the poverty population has not occurred despite growth in the elderly segment of the overall population. Concerning turnover in the poverty population, we find that despite poverty theories emphasizing persistence, recurrent poverty is relatively rare and poverty is not generally passed from one generation to the next. Poverty prevention has come from both economic growth and government transfers; however, inequality in economic growth has contributed to poverty. With the proportion of elderly and female- headed households likely to continue at a high level into the future, poverty rates are also likely to remain high unless government transfers are increased.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66979/2/10.1177_000271628547900103.pd
Proposal of serovars 17 and 18 of Actinobacillus pleuropneumoniae based on serological and genotypic analysis
The aim of this study was to investigate isolates of Actinobacillus pleuropneumoniae previously designated serologically either as NT or as ‘K2:07’, which did not produce serovar-specific amplicons in PCR assays.
We used whole genome sequencing to identify the capsule (CPS) loci of six previously designated biovar 1 non-typable (NT) and two biovar 1 ‘K2:O7’ isolates of A. pleuropneumoniae from Denmark, as well as a recent biovar 2 NT isolate from Canada. All of the NT isolates have the same six-gene type I CPS locus, sharing common cpsABC genes with serovars 2, 3, 6, 7, 8, 9, 11 and 13. The two ‘K2:O7’ isolates contain a unique three-gene type II CPS locus, having a cpsA gene similar to that of serovars 1, 4, 12, 14 and 15. The previously NT isolates share the same O-antigen genes, found between erpA and rpsU, as serovars 3, 6, 8, and 15. Whereas the ‘K2:O7’ isolates, have the same O-antigen genes as serovar 7, which likely contributed to their previous mis-identification. All of the NT and ‘K2:O7’ isolates have only the genes required for production of ApxII (apxIICA structural genes, and apxIBD export genes).
Rabbit polyclonal antisera raised against representative isolates with these new CPS loci demonstrated distinct reactivity compared to the 16 known serovars. The serological and genomic results indicate that the isolates constitute new serovars 17 (previously NT) and 18 (previously ‘K2:O7’). Primers designed for amplification of specific serovar 17 and 18 sequences for molecular diagnostics will facilitate epidemiological tracking of these two new serovars of A. pleuropneumoniae
Recommended from our members
The Long-Term Clinical Outcomes Following Autogenous Bone Grafting for Large-Volume Defects of the Knee: 12- to 21-Year Follow-Up
Objective: We report the long-term clinical outcomes of patients who underwent autogenous bone grafting of large-volume osteochondral defects of the knee due to osteochondritis dessicans (OCD) and osteonecrosis (ON). This is the companion report to one previous published on the biological response. We hypothesized that these grafts would integrate with host bone and the articular surface would form fibrocartilage providing an enduring clinical benefit. Design: Three groups (patients/knees) were studied: OCD without a fragment (n = 12/13), OCD with a partial fragment (n = 14/16), and ON (n = 25/26). Twenty-five of 52 patients were available for clinical follow-up between 12 and 21 years. Electronic medical records provided comparison clinical information. In addition, there were plain film radiographs, MRIs, plus repeat arthroscopy and biopsy on 14 patients. Results: Autogenous bone grafts integrated with the host bone. MRI showed soft tissue covering all the grafts at long-term follow-up. Biopsy showed initial surface fibrocartilage that subsequently converted to fibrocartilage and hyaline cartilage at 20 years. OCD patients had better clinical outcomes than ON patients. No OCD patients were asymptomatic at anytime following surgery. Half of the ON patients came to total knee replacement within 10 years. Conclusions: Autogenous bone grafting provides an alternative biological matrix to fill large-volume defects in the knee as a singular solution integrating with host bone and providing an enduring articular cartilage surface. The procedure is best suited for those with OCD. The treatment for large-volume articular defects by this method remains salvage in nature and palliative in outcome
Recommended from our members
The Biological Response following Autogenous Bone Grafting for Large-Volume Defects of the Knee: Index Surgery through 12 to 21 Years’ Follow-up
Objective: This report focuses on the biological events occurring at various intervals following autogenous bone grafting of large-volume defects of the knee joint’s femoral condyle secondary to osteochondritis dissecans (OCD) or osteonecrosis (ON). It was hypothesized that the autogenous bone graft would integrate and the portion exposed to the articular surface would form fibrocartilage, which would endure for years. Methods: Between September 29, 1987 and August 8, 1994, there were 51 patients treated with autogenous bone grafting for large-volume osteochondral defects. Twenty-five of the 51 patients were available for long-term follow-up up to 21 years. Patient follow-up was accomplished by clinical opportunity and intentional research. Videotapes were available on all index surgeries for review and comparison. All had preoperative and postoperative plain film radiographs. Long-term follow-up included MRI up to 21 years. Second-look arthroscopy and biopsy were obtained on 14 patients between 8 weeks and 20 years. Results: Radiological assessment showed the autogenous bone grafts integrated with the host bone. The grafts retained the physical geometry of the original placement. MRI showed soft tissue covering the grafts in all cases at long-term follow-up. Interval biopsy showed the surface covered with fibrous tissue at 8 weeks and subsequently converted to fibrocartilage with hyaline cartilage at 20 years. Conclusion: Autogenous bone grafting provides a matrix for large osteochondral defects that integrates with the host bone and results in a surface repair of fibrocartilage and hyaline cartilage that can endure for up to 20 years
Mutation rate dynamics reflect ecological change in an emerging zoonotic pathogen.
Funder: Raymond and Beverly Sackler FoundationFunder: Isaac Newton TrustFunder: Newnham College, University of CambridgeFunder: Medical Research CouncilMutation rates vary both within and between bacterial species, and understanding what drives this variation is essential for understanding the evolutionary dynamics of bacterial populations. In this study, we investigate two factors that are predicted to influence the mutation rate: ecology and genome size. We conducted mutation accumulation experiments on eight strains of the emerging zoonotic pathogen Streptococcus suis. Natural variation within this species allows us to compare tonsil carriage and invasive disease isolates, from both more and less pathogenic populations, with a wide range of genome sizes. We find that invasive disease isolates have repeatedly evolved mutation rates that are higher than those of closely related carriage isolates, regardless of variation in genome size. Independent of this variation in overall rate, we also observe a stronger bias towards G/C to A/T mutations in isolates from more pathogenic populations, whose genomes tend to be smaller and more AT-rich. Our results suggest that ecology is a stronger correlate of mutation rate than genome size over these timescales, and that transitions to invasive disease are consistently accompanied by rapid increases in mutation rate. These results shed light on the impact that ecology can have on the adaptive potential of bacterial pathogens
Nanoparticles within WWTP sludges have minimal impact on leachate quality and soil microbial community structure and function
One of the main pathways by which engineered nanoparticles (ENPs) enter the environment is through land application of waste water treatment plant (WWTP) sewage sludges. WWTP sludges, enriched with Ag and ZnO ENPs or their corresponding soluble metal salts during anaerobic digestion and subsequently mixed with soil (targeting a final concentration of 1400 and 140 mg/kg for Zn and Ag, respectively), were subjected to 6 months of ageing and leaching in lysimeter columns outdoors. Amounts of Zn and Ag leached were very low, accounting for <0.3% and <1.4% of the total Zn and Ag, respectively. No differences in total leaching rates were observed between treatments of Zn or Ag originally input to WWTP as ENP or salt forms. Phospholipid fatty acid profiling indicated a reduction in the fungal component of the soil microbial community upon metal exposure. However, overall, the leachate composition and response of the soil microbial community following addition of sewage sludge enriched either with ENPs or metal salts was very similar
Developmental programming of cardiovascular dysfunction by prenatal hypoxia and oxidative stress.
Fetal hypoxia is a common complication of pregnancy. It has been shown to programme cardiac and endothelial dysfunction in the offspring in adult life. However, the mechanisms via which this occurs remain elusive, precluding the identification of potential therapy. Using an integrative approach at the isolated organ, cellular and molecular levels, we tested the hypothesis that oxidative stress in the fetal heart and vasculature underlies the molecular basis via which prenatal hypoxia programmes cardiovascular dysfunction in later life. In a longitudinal study, the effects of maternal treatment of hypoxic (13% O(2)) pregnancy with an antioxidant on the cardiovascular system of the offspring at the end of gestation and at adulthood were studied. On day 6 of pregnancy, rats (n = 20 per group) were exposed to normoxia or hypoxia ± vitamin C. At gestational day 20, tissues were collected from 1 male fetus per litter per group (n = 10). The remaining 10 litters per group were allowed to deliver. At 4 months, tissues from 1 male adult offspring per litter per group were either perfusion fixed, frozen, or dissected for isolated organ preparations. In the fetus, hypoxic pregnancy promoted aortic thickening with enhanced nitrotyrosine staining and an increase in cardiac HSP70 expression. By adulthood, offspring of hypoxic pregnancy had markedly impaired NO-dependent relaxation in femoral resistance arteries, and increased myocardial contractility with sympathetic dominance. Maternal vitamin C prevented these effects in fetal and adult offspring of hypoxic pregnancy. The data offer insight to mechanism and thereby possible targets for intervention against developmental origins of cardiac and peripheral vascular dysfunction in offspring of risky pregnancy
Comparative sequence analysis of the capsular polysaccharide loci of Actinobacillus pleuropneumoniae serovars 1-18, and development of two multiplex PCRs for comprehensive capsule typing
Problems with serological cross-reactivity have led to development of a number of PCRs (individual and multiplex) for molecular typing of Actinobacillus pleuropneumoniae, the causative agent of porcine pleuropneumonia. Most of these assays were developed for detection of specific amplicons within capsule biosynthetic genes before the availability of complete sequences for the different serovars. Here we describe comparative analysis of the complete capsular loci for all 18 serovars of A. pleuropneumoniae, and development of two multiplex PCRs for comprehensive capsule typing of this important pig pathogen
- …