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Biomedical subjects

A P Johnson

Publications and source records attributed to A P Johnson.

At least 19 recordsLinked to original sources

Study on spontaneous cerebrospinal fluid rhinorrhoea: its aetiology and management.

The aim of this study was to identify the common features in a study group of patients with spontaneous cerebrospinal fluid (CSF) rhinorrhoea, to develop a hypothesis to explain the cause of this condition and to investigate the outcome of surgical techniques adopted to repair the leak. In this retrospective study the authors have reviewed all the cases of spontaneous CSF leaks attending and receiving treatment from the otolaryngology department of Queen Elizabeth Hospital, Birmingham, from 1992 to 2002. Of 34 patients with CSF leaks, 15 were spontaneous in nature and formed the study group. Of these 15 patients, 14 were female; with ages ranging from 37 to 70 years and a median age of 50 years. All the female patients were overweight with a body mass index (BMI) >24.9 and, of these, nine were considered obese with a BMI >30. It was attempted to identify common factors in the study group and it was evident that female sex, obesity and age played a key role in this condition. The follow-up period ranged from two to 98 months. Thirteen patients were asymptomatic but two patients remained symptomatic, one of these despite repeated surgical intervention.

Adult↗

Community and hospital spread of Escherichia coli producing CTX-M extended-spectrum beta-lactamases in the UK.

OBJECTIVES: During 2003, the Health Protection Agency's Antibiotic Resistance Monitoring and Reference Laboratory began to receive isolates of Escherichia coli for confirmation of extended-spectrum beta-lactamase production with a phenotype implying a CTX-M-type beta-lactamase, i.e. MICs of cefotaxime > or = 8-fold higher than MICs of ceftazidime. Many were referred as being from community patients. We examined 291 CTX-M-producing isolates from the UK and investigated the genetic basis of their phenotype. METHODS: PCR was used to detect alleles encoding CTX-M enzymes and to assign these to their blaCTX-M phylogenetic groups. Selected alleles were sequenced. Producers were compared by analysis of banding patterns generated by pulsed-field gel electrophoresis of XbaI-digested genomic DNA. MICs were determined by an agar dilution method or by Etest. RESULTS: Of 291 CTX-M-producing E. coli isolates studied from 42 UK centres, 70 (24%) were reportedly from community patients, many of whom had only limited recent hospital contact. Community isolates were referred by 12 centres. Two hundred and seventy-nine (95.9%) producers contained genes encoding group 1 CTX-M enzymes and 12 contained blaCTX-M-9-like alleles. An epidemic CTX-M-15-producing strain was identified, with 110 community and inpatient isolates referred from six centres. Representatives of four other major strains also produced CTX-M-15, as did several sporadic isolates examined. Most producers were multi-resistant to fluoroquinolones, trimethoprim, tetracycline and aminoglycosides as well as to non-carbapenem beta-lactams. CONCLUSIONS: CTX-M-producing E. coli are a rapidly developing problem in the UK, with CTX-M-15 particularly common. The diversity of producers and geographical scatter of referring laboratories indicates wide dissemination of blaCTX-M genes. Because of the public health implications, including for the treatment of community-acquired urinary tract infections, the spread of these strains--and CTX-M-15 beta-lactamase in particular--merits close monitoring.

Alleles↗

Pseudoaneurysm after total pharyngolaryngectomy with jejunal graft insertion: two different presentations.

Pharyngeal reconstruction after total pharyngolaryngectomy using a jejunal graft is now a common procedure in head and neck oncological surgery. The vascular supply of this graft comes from the anastomosis between a branch of the mesentric artery and a branch of the external carotid artery. We report two cases of pseudoaneurysm, one at the site of ligation of the lingual artery and the other at the site of arterial anastomosis. One presented with dramatic hematemesis and was managed by the interventional radiologist, and the second presented with a pulsating neck mass and required a surgical revision. In both cases, the jejunal graft survived.

Aged↗

Reliability of routine disc susceptibility testing by the British Society for Antimicrobial Chemotherapy (BSAC) method.

OBJECTIVES: To ascertain the agreement between MICs determined at a central laboratory, and susceptible, intermediate and resistant categorizations based on zone diameters recorded at diagnostic laboratories using the BSAC standardized method. METHODS: Standardized disc susceptibility tests were performed at sentinel laboratories in three surveys, with MIC tests performed on the collected isolates at a reference laboratory. The organisms comprised over 3300 Enterobacteriaceae, Acinetobacter spp., pseudomonads, staphylococci and enterococci, with over 29 000 antibiotic/organism tests in total. RESULTS: More than 90% of the antibiotic/organism combinations classed as susceptible by disc tests in the sentinel laboratories were confirmed by MIC testing. Disagreements were more frequent where disc tests indicated resistance, with half of the piperacillin/tazobactam resistance and one-third of the cephalosporin resistance found in Enterobacteriaceae by disc tests not being confirmed, and with three-quarters of teicoplanin resistance in enterococci not confirmed. None of the few apparent cases of meropenem resistance in Enterobacteriaceae or linezolid, quinupristin/dalfopristin or vancomycin resistance in staphylococci were confirmed by MIC testing. When disagreements were found between disc- and MIC-based categorization, MICs were commonly, although not invariably, one to three doubling dilutions above or below the breakpoint. However, many of the disagreements where MICs were three or more dilutions from the breakpoint were not seen when disc tests were repeated in the central laboratory. CONCLUSIONS: The BSAC disc method seems adequate for confirming susceptibility to guide therapy and to monitor resistance trends. Nevertheless, there must be concern about the over-estimation of many resistances, and frequent zone:MIC disagreements for isolates with borderline susceptibility.

Bacteria↗

Activity of daptomycin against multi-resistant Gram-positive bacteria including enterococci and Staphylococcus aureus resistant to linezolid.

The activity of daptomycin was assessed against 545 isolates of Gram-positive bacteria including enterococci, coagulase-positive and -negative staphylococci, beta-haemolytic streptococci, viridans streptococci and coryneforms. The panel of isolates was biased towards those with resistance to first-line antimicrobial agents and included linezolid-resistant enterococci and Staphylococcus aureus. MICs of daptomycin were < or =1mg/l for all the staphylococci, streptococci, and coryneforms, except for two isolates of Corynebacterium aquaticum, for which MICs were 8 mg/l. Daptomycin MICs were < or =2 and < or =4 mg/l for Enterococcus faecalis and Enterococcus faecium, respectively.

Acetamides↗

Pulp mill process closure: a review of global technology developments and mill experiences in the 1990s.

The impact of effluent discharges continues to be an important issue for the pulp manufacturing industry. Considerable progress has been made in pollution prevention to minimize waste generation, so-called manufacturing "process closure." Since the mid-1980s many important technologies have been developed and implemented, many of these in response to organochlorine concerns. Zero effluent operation is now a reality for a few bleached chemi-thermomechanical pulp (BCTMP) pulp mills. In kraft pulp manufacturing, important developments include widespread adoption of new cooking techniques, oxygen delignification, closed screening, improved process control, new bleaching methods, and systems that minimize pulping liquor losses. Coupled to this is a commitment to reduce water use and maximize reuse of in-mill process streams. Some companies pursued bleach plant closure, and many have been successful in eliminating a portion of their bleaching wastewaters. However, the difficulties inherent in closing bleach plants are considerable. For many mills the optimal solution has been found to be a high degree of closure coupled with external biological treatment of the remaining process effluent. No bleach plants at papergrade bleached kraft mills are known to be operating effluent-free on a continuous basis. This paper reviews the important worldwide technological developments and mill experiences in the 1990s that were focused on minimizing environmental impacts of pulp manufacturing operations.

Industrial Waste↗

Emergence of a fluoroquinolone-resistant strain of Streptococcus pneumoniae in England.

OBJECTIVE: To determine the epidemiological relationship between pneumococci of serotype 9V, with reduced susceptibility to ciprofloxacin, penicillin and erythromycin, referred to the Reference Laboratory during 1997-2001. METHODS: Isolates were characterized by multilocus sequence typing (MLST), PFGE, and sequencing of parC and gyrA. Relevant clinical data were sought. RESULTS: Forty-eight isolates were received from nine laboratories in England, but 35 (73%) were from one laboratory in Birmingham, and were mostly from elderly patients receiving ofloxacin or ciprofloxacin for respiratory infections. There were two quinolone resistance phenotypes, with ciprofloxacin, moxifloxacin and gemifloxacin MICs of 8-32, 0.5-1 and 0.125-0.25 mg/L, and 64-256, 4-16 and 1-4 mg/L, respectively. Each of three isolates from the former group had mutations in parC, whereas each of nine isolates from the more resistant group had mutations in both parC and gyrA. Several also had increased quinolone efflux. Typing of 27 quinolone-resistant isolates showed that eight were indistinguishable from the epidemic Spain9V-3 (ST156) clone, while the remainder belonged to a novel but related type (ST609), that differed from Spain9V-3 at 2/7 alleles (2 bp changes in aroE and 1 bp change in gdh). Both MLST types were represented among isolates with high- and low-level quinolone resistance. Three of five serotype 9V isolates from Birmingham, with reduced susceptibility to penicillin and erythromycin, and ciprofloxacin MICs of 1-2 mg/L, belonged to MLST type ST609, while another was indistinguishable from the Spain9V-3 clone. Review of records of 32 patients from Birmingham indicated that some isolates were nosocomial, whereas others were acquired in the community. CONCLUSIONS: In the late 1990s, a quinolone-resistant strain, clonally related to Spain9V-3, emerged in England, principally in Birmingham.

Aged↗

Susceptibility of Gram-positive bacteria from ICU patients in UK hospitals to antimicrobial agents.

Microbiologists in 25 sentinel laboratories were each asked to refer up to 100 clinically-significant Gram-positive bacteria isolated from consecutive intensive care unit (ICU) patients. A total of 1595 isolates were collected from patients in 23 hospitals; these included Staphylococcus aureus (47.6%), coagulase-negative staphylococci (CNS) (30.6%), enterococci (14.3%), pneumococci (2.8%) and other streptococci (3.5%). A few coryneforms, other bacilli and a Nocardia sp. were also collected. Rates of oxacillin resistance among S. aureus and CNS isolates were 59.3 and 78.5%, respectively. Vancomycin-resistant S. aureus were not detected, although two isolates (0.3%) were resistant to teicoplanin [minimum inhibitory concentrations (MICs) 8 mg/L]. In contrast, 13.7% of CNS were teicoplanin resistant (MICs 8-32 mg/L) and 1.2% were resistant to vancomycin. Among the enterococci, 72.5% were Enterococcus faecalis and 24.5% were Enterococcus faecium, the remainder including isolates of Enterococcus casseliflavus or Enterococcus gallinarum. Eighteen percent of E. faecium isolates were vancomycin-resistant, compared with only 3% of E. faecalis isolates. Rates of high-level gentamicin resistance in E. faecalis and E. faecium were 40 and 25%, respectively. Nine percent of pneumococci and streptococci were resistant to penicillin, with 7 and 11%, respectively, resistant to erythromycin. None of the isolates showed resistance to linezolid, with the MICs for the entire study population falling in the range of 0.5-4 mg/L.

Coagulase↗

In vitro activity of piperacillin/tazobactam and other broad-spectrum antibiotics against bacteria from hospitalised patients in the British Isles.

Piperacillin/tazobactam is used for empirical therapy of severe and complex infections. We assessed its activity, 9 years after launch, against consecutive, clinically significant isolates from in-patients in UK and Ireland. Standardised disc susceptibility tests were performed on 5031 isolates at 28 hospitals. For quality assurance purposes, 5% of these isolates were collected centrally for MIC tests, as were those with exceptional resistances. Compared with a similar pre-launch survey in 1991, there were major increases in the proportions of Staphylococcus aureus, Pseudomonas aeruginosa, beta-haemolytic streptococci and Enterococcus faecium isolates collected, balanced by decreases in Escherichia coli, Proteus mirabilis and coagulase-negative staphylococci. These changes in species prevalence mostly favoured organisms with inherent resistance(s) or-in the case of S. aureus-reflected the massive increase of MRSA, up from 0.7% of all isolates in 1991 to 14.8% in 2001. Based on the disc tests, piperacillin/tazobactam retained activity against 87% of Enterobacteriaceae isolates, 95% of P. aeruginosa, 99% of streptococci and 96% of Enterococcus faecalis. Resistance nevertheless had increased since 1991 in E. coli from 4 to 10%, Klebsiella spp. (5 to 21%) and in AmpC-inducible Enterobacteriaceae (17 to 23%), though not in P. mirabilis or P. aeruginosa. MIC tests confirmed most of the piperacillin/tazobactam resistance found by disc tests in Enterobacter spp., but indicated susceptibility for about half of the E. coli isolates recorded as resistant in disc tests. This situation might be remedied by reducing the zone breakpoint, but this would increase the "false susceptible" rate unacceptably. Thus, if disc tests suggest that an isolate is marginally resistant to piperacillin/tazobactam and the drug is sought as therapy, it is recommended that MIC be determined with, e.g., an Etest.

Bacteria↗

Emerging linezolid-resistant Enterococcus faecalis and Enterococcus faecium isolated from two Austrian patients in the same intensive care unit.

Of two patients in the same intensive care unit who were treated with linezolid, one yielded linezolid-resistant Enterococcus faecalis, whereas the other yielded linezolid-resistant Enterococcus faecium. In each case, molecular typing indicated that the resistant isolates were related to linezolid-susceptible isolates from the same patient, but differed from them by the same G2576U ribosomal RNA mutation. This is the first clinical case report of emerging resistance to linezolid among Enterococcus faecalis and also the first report of resistance involving vancomycin-susceptible rather than vancomycin-resistant enterococci. The linezolid-resistant isolates showed cross-resistance to the experimental oxazolidinone AZD2563, suggesting that oxazolidinone resistance might be a class effect.

Acetamides↗

Who performs thyroid surgery: a review of current otolaryngological practice.

Thyroid surgery has been traditionally a general surgical practice, but recently more otolaryngologists have been offering a thyroid service. We have quantified thyroid surgery performed by the different specialties, and looked more closely at the practice of otolaryngologists. Data was obtained from the Department of Health for UK thyroid surgery in all specialties for the year 1998-99 and validated against a survey of members of the British Association of Otolaryngologists-Head & Neck Surgeons (BAO-HNS). The use of investigations of a simple clinical case (solitary thyroid nodule) was compared with best practice. General surgeons still perform the majority of thyroid surgery (83%) but ENT surgeons now perform significant numbers (15.4% of all cases), which translates to 1499 cases per annum. A total of 102 BAO-HNS members were performing thyroid surgery with an average case-load of 19.1 per year. In total, 35% of ENT surgeons see thyroid patients in multidisciplinary clinics. The choice of investigation is consistent with European guidelines. ENT surgeons are doing significant amounts of thyroid surgery and the numbers appear to be increasing. The formation of multidisciplinary teams including general surgeons and otolaryngologists who are committed to subspecialization can only improve both training and treatment outcomes.

General Surgery↗

Haemangiopericytoma of the submental region.

Haemangiopericytoma refers to an uncommon vascular/perivascular neoplasm of which a minority of cases arise in the head and neck. It comprises a group of lesions with marked clinical and pathological heterogeneity and a lack of positive criteria by which to make a definitive diagnosis. We describe an unusual case of such a tumour in the submental region, review its pathological features and discuss issues in management and prognosis.

Head and Neck Neoplasms↗

NF kappa B and AP-1 mediate transcriptional responses to oxidative stress in skeletal muscle cells.

The ability to induce cellular defense mechanisms in response to environmental challenges is a fundamental property of eukaryotic and prokaryotic cells. We have previously shown that oxidative challenges lead to an increase in antioxidant enzymes, particularly glutathione peroxidase (GPx) and catalase (CAT), in mouse skeletal muscle. The focus of the current studies is the transcriptional regulatory mechanisms responsible for these increases. Sequence analysis of the mouse GPx and CAT genes revealed putative binding motifs for NF kappa B and AP-1, transcriptional regulators that are activated in response to oxidative stress in various tissues. To test whether NF kappa B or AP-1 might be mediating the induction of GPx and CAT in muscle cells subjected to oxidative stress, we first characterized their activation by pro-oxidants. Electrophoretic mobility shift assays showed that oxidative stress led to increases in the DNA binding of NF kappa B in differentiated muscle cells. The NF kappa B complexes included a p50/p65 heterodimer, a p50 homodimer, and a p50/RelB heterodimer. AP-1 was also activated, but with slower kinetics than that of NF kappa B. The major component of the AP-1 complexes was a heterodimer composed of c-jun/fos. To test for redox regulation of NF kappa B- or AP-1-dependent transcriptional activation, muscle cells expressing either kappa B/luciferase or TRE/luciferase reporter constructs were subjected to oxidative stress. Pro-oxidant treatment resulted in increased luciferase activity in cells expressing either construct. To test whether NF kappa B mediates oxidant-induced increases of GPx and CAT expression, we transfected cells with either a transdominant inhibitor (I kappa B alpha) or a dominant-negative inhibitor (Delta SP) of NF kappa B. Both inhibitors blocked the induction of antioxidant gene expression by more than 50%. In summary, our results suggest that NF kappa B and AP-1 are important mediators of redox-responsive gene expression in skeletal muscle, and that at least NF kappa B is actively involved in the upregulation of the GPx and CAT in response to oxidative stress.

Animals↗

Antimicrobial susceptibility of Gram-positive bacteria: what's current, what's anticipated?

Changing patterns of pathogens and antibiotic susceptibility present clinicians with difficult choices for antimicrobial prescribing. In particular, multiresistant staphylococci, enterococci and pneumococci present problems in many settings. The number of predictably active antimicrobials is decreasing in many centres, with significant consequences for both patients and society as a whole. New antimicrobial options have been few in recent years and several promising quinolones have been compromised by formulation and/or toxicity issues. Nevertheless, the recent introduction of linezolid and quinupristin/dalfopristin provides clinicians with valuable new options against Gram-positive cocci. These options should further increase with the likely introduction of daptomycin, oritavancin and tigilcycline. A range of surveillance programmes helps monitor the ever-changing patterns of resistance and thus guides clinicians in their empirical prescribing. Empirical use of powerful newer agents may be justifiable in seriously ill patients in those settings, units and countries where there is a substantial background rate of resistance.

Acetamides↗