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K Jones

Publications and source records attributed to K Jones.

At least 19 recordsLinked to original sources
PubMed2006

Assessing isocyanate exposures in polyurethane industry sectors using biological and air monitoring methods.

Isocyanates, as a chemical group, are considered to be the biggest cause of occupational asthma in the UK. Monitoring of airborne exposures to total isocyanate is costly, requiring considerable expertise, both in terms of sample collection and chemical analysis and cannot be used to assess the effectiveness of protection from wearing respiratory protective equipment (RPE). Biological monitoring by analysis of metabolites in urine can be a relatively simple and inexpensive way to assess exposure to isocyanates. It may also be a useful way to evaluate the effectiveness of control measures in place. In this study biological and inhalation monitoring were undertaken to assess exposure in a variety of workplaces in the non-motor vehicle repair sector. Companies selected to participate in the survey included only those judged to be using good working practices when using isocyanate formulations. This included companies that used isocyanates to produce moulded polyurethane products, insulation material and those involved in industrial painting. Air samples were collected by personal monitoring and were analysed for total isocyanate content. Urine samples were collected soon after exposure and analysed for the metabolites of different isocyanate species, allowing calculation of the total metabolite concentration. Details of the control measures used and observed contamination of exposed skin were also recorded. A total of 21 companies agreed to participate in the study, with exposure measurements being collected from 22 sites. The airborne isocyanate concentrations were generally very low (range 0.0005-0.066 mg m(-3)). A total of 50 of the 70 samples were <0.001 mg m(-3), the limit of quantification (LOQ), therefore samples below the LOQ were assigned a value of 1/2 LOQ (0.0005 mg m(-3)). Of the 70 samples, 67 were below the current workplace exposure limit of 0.02 mg m(-3). The highest inhalation exposures occurred during spray painting activities in a truck manufacturing company (0.066 mg m(-3)) and also during spray application of polyurethane foam insulation (0.023 mg m(-3)). The most commonly detected isocyanate in the urine was hexamethylene diisocyanate, which was detected in 21 instances. The geometric mean total isocyanate metabolite concentration for the dataset was 0.29 micromol mol(-1) creatinine (range 0.05-12.64 micromol mol(-1) creatinine). A total of 23 samples collected were above the agreed biological monitoring guidance value of 1.0 micromol mol(-1) creatinine. Activities that resulted in the highest biological monitoring results of the dataset included mixing and casting of polyurethane products (12.64 micromol mol(-1) creatinine), semi-automatic moulding (4.80 micromol mol(-1) creatinine) and resin application (3.91 micromol mol(-1) creatinine). The biological monitoring results show that despite low airborne isocyanate concentrations, it was possible to demonstrate biological uptake. This tends to suggest high sensitivity of the biological monitoring method and/or that in some instances the RPE being used by operators was not effective or that absorption may have occurred via dermal or other routes of exposure. This study demonstrates that biological monitoring is a useful tool when assessing worker exposure to isocyanates, providing a more complete picture on the efficacy of control measures in place than is possible by air monitoring alone. The results also demonstrated that where control measures were judged to be adequate, most biological samples were close to or < 1 micromol mol(-1) creatinine, the agreed biological monitoring benchmark.

Air Pollutants, Occupational↗
PubMed2006

Biological monitoring for trimethylbenzene exposure: a human volunteer study and a practical example in the workplace.

This paper presents data from both a human volunteer study looking at exposure to 1,3,5-trimethylbenzene (TMB) and an occupational hygiene study of a printing firm using screen wash containing technical grade TMB. The biomarkers measured were TMB in blood and breath, and urinary dimethylbenzoic acids (DMBAs). The volunteer (N = 4) study showed that TMB was rapidly absorbed into the bloodstream reaching a mean level of 0.85 micromol l(-1) during a 4 h exposure to 25 p.p.m. TMB. There was little decline 1 h post-exposure possibly indicating storage of TMB in adipose tissue. Breath TMB levels peaked within an hour of exposure commencing and averaged 137 nmol l(-1) during exposure. Elimination of TMB in breath was biphasic with an initial half-life of 60 min. Peak excretion of urinary DMBA occurred 4-8 h after the end of exposure and averaged 40 mmol mol(-1) creatinine. Elimination of DMBA in urine was biphasic with half-lives of 13 and 60 h indicating that accumulation of body burden throughout the working week is likely if exposure is repeated. The occupational hygiene study demonstrated an excellent correlation between personal air TMB levels and post-shift urinary DMBA levels (r = 0.997) collected on the third working day. The regression equation from this study indicates that 8 h exposure to 25 p.p.m. TMB would result in a urinary DMBA level of 206 mmol mol(-1) creatinine. All workers showed pre-shift levels of DMBA from exposure to TMB on previous days. Both urinary DMBA and breath TMB levels can be used as biomarkers of TMB exposure. Urine samples should be taken post-shift towards the end of the working week as significant body burden accumulation throughout the working week can be expected. Breath sampling is more suited to task or single-shift monitoring.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2006

'Coming out' with Alzheimer's disease: changes in awareness during a psychotherapy group for people with dementia.

This paper forms part of the second phase of a project looking at those changes that occurred for participants during a series of time-limited psychotherapy groups for people with dementia. Using the Assimilation of Problematic Experiences Scale (APES), the accounts of one participant (Robert) are analyzed across the course of the group. Robert moves from a position in which he wards off awareness that he has dementia of the Alzheimer's type, to being able to joke about having brain changes that are symptomatic of the illness. This change in his discourse about Alzheimer's disease was accompanied by an increase in Robert's levels of affect. However, reflecting on the changes that had occurred for him, Robert commented that before he came to the group he had been frightened, thinking that 'I'm going crazy?...?what am I going to be like in another five years?'. For Robert, coming to the group had meant that this fear had been replaced by the knowledge that he was not alone. In the light of the move towards early diagnosis, the importance of this model of change in awareness as a means of increasing understanding of the process of emotional development is discussed.'...?but I think that a lot of people who I have met who have come out about Alzheimer's were quite shocked because I said that. It did help, it may not have helped others, but I suppose that it helps overcome a feeling of being different.'Janet, session six.

Aged↗
PubMed2006

Informal care as relationship: the case of the Magnificent Seven.

Continual and/or repetitive informal caring and the part childhood, developmental and socially constructed identity play roles in adult informal care, form the background to the questions of why individuals gravitate toward such relationships and why they often continue to care in the face of overwhelming obstacles. A synthesis of the literature is presented, leading to personal histories as a method of discovery. The Biographic Narrative Interpretive Method's minimalist interview technique is put forth as the key data-gathering event. Reflecting teams, underpinned by hermeneutics or interpretive phenomenology, are used for the analyses. Data from in-depth, biographic interviews with two informal carers (a mother and her adult son) from a seven-member, three-generational family are presented. The study reveals that this family defines disability as a status that they share in common: disability demonstrates relationships and keeps the family together, but discourages mobility. It is suggested that often-unmet childhood needs propelled these particular individuals into demonstrating those needs as adults by assuming informal care relationships. The case is made that their biographies impact upon their management of health and enduring illnesses within caring roles. Further biographic research within the caring profession is recommended.

Caregivers↗
PubMed2005

Exposure to antineoplastic drugs in two UK hospital pharmacy units.

STUDY OBJECTIVES: To carry out an environmental and biological monitoring study in two UK hospital pharmacy units involved in the preparation of antineoplastic drugs. PARTICIPANTS AND METHODS: The two units studied used isolators for drug preparation. One used isolators operating at positive pressure relative to external atmospheric pressure, whereas the other used negative pressure isolators. Monitoring utilized the measurements of methotrexate, ifosfamide, cyclophosphamide and platinum reflecting the platino-coordinated drugs, such as cisplatin and carboplatin. Personal and static atmospheric and floor wipe samples were collected together with preshift and post-shift urine samples over a 4-day consecutive monitoring period. During the study period both units operated to their normal procedures. RESULTS: Measurable amounts of cytotoxic drugs were detected on the floors of both units and on the disposable gloves worn by staff preparing the drugs. There was also evidence in both units of some very low-level drug absorption from urine measurements, using the most sensitive analytical technique of platinum analysis. The absorption of platinum containing drugs in the unit using negative-pressure isolators was significantly higher, even though less platinum containing drug was prepared per day. Urine measurements in both units were below the detection limit for the other measured drugs. Although the unit using positive-pressure isolators handled daily approximately five times the drug quantities handled with the negative pressure unit, the general levels of external contamination and urine measurements did not reflect this difference. Comparison of the relative levels of glove and floor contamination between the two units was not clear-cut and appeared to depend on the specific cytotoxic drug being monitored. CONCLUSIONS: The levels of external contamination on the floor and gloves, and absorbed dose from urine measurements found in this study showed considerable improvement over many earlier, non-UK studies using comparable exposure measurements. These earlier studies were in facilities using laminar flow/microbiological safety cabinets and where staff were likely to be involved in both drug preparation and administration. Our data did not suggest that the differential pressure of the isolator to the pharmacy atmosphere was an overarching factor in the risk of operator exposure under normal operation. There remains a need to investigate the sources of the low-level drug contamination found in the pharmacies even when using isolators to prepare cytotoxic drugs. This study, and related studies of hospital oncology ward staff, appear to be the only recent UK studies of occupational cytotoxic drug exposure using environmental and biological monitoring techniques.

Air Pollution, Indoor↗
PubMed2005

An appraisal of options of the training and education of Professionals Complementary to Dentistry.

The training and education of Professionals Complementary to Dentistry (PCDs) has become a topic of close scrutiny and much debate in the recent past, particularly with the introduction of enhanced duties and compulsory registration of some groups. This paper will describe the background to, the conduct of and the findings from a workshop held to explore innovative approaches to the education and training of PCDs in the United Kingdom. Existing systems of training and education of PCDs will be reviewed through the exploration of published literature and through the collection of primary data from interviews with key personnel both in the UK and internationally. An option appraisal is described which identified the elements common to all training approaches, used the elements as the basis for innovative training options, and explored the perceived advantages and disadvantages of each option through focus group discussions at a one-day workshop. A model for the training and education of PCDs is described that maintains existing PCD roles, but offers a broader range of entry points to training, settings for training and that builds upon existing skills to facilitate progression through the PCD roles.

Dental Auxiliaries↗
PubMed2005

Atoh1 null mice show directed afferent fiber growth to undifferentiated ear sensory epithelia followed by incomplete fiber retention.

Inner ear hair cells have been suggested as attractors for growing afferent fibers, possibly through the release of the neurotrophin brain-derived neurotrophic factor (BDNF). Atoh1 null mice never fully differentiate hair cells and supporting cells and, therefore, may show aberrations in the growth and/or retention of their innervation. We investigated the distribution of cells positive for Atoh1- or Bdnf-mediated beta-galactosidase expression in Atoh1 null and Atoh1 heterozygotic mice and correlated the distribution of these cells with their innervation. Embryonic day (E) 18.5 Atoh1 null and heterozygotic littermates show Atoh1- and BDNF-beta-galactosidase-positive cells in comparable distributions in the canal cristae and the cochlea apex. Atoh1-beta-galactosidase-positive but only occasional Bdnf-beta-galactosidase-positive cells are found in the utricle, saccule, and cochlea base of Atoh1 null mutant mice. Absence of Bdnf-beta-galactosidase expression in the utricle and saccule of Atoh1 null mice is first noted at E12.5, a time when Atoh1-beta-galactosidase expression is also first detected in these epithelia. These data suggest that expression of Bdnf is dependent on ATOH1 protein in some but does not require ATOH1 protein in other inner ear cells. Overall, the undifferentiated Atoh1- and Bdnf-beta-galactosidase-positive cells show a distribution reminiscent of that in the six sensory epithelia in control mice, suggesting that ear patterning processes can form discrete patches of Atoh1 and Bdnf expression in the absence of ATOH1 protein. The almost normal growth of afferent and efferent fibers in younger embryos suggests that neither fully differentiated hair cells nor BDNF are necessary for the initial targeted growth of fibers. E18.5 Atoh1 null mice have many afferent fibers to the apex of the cochlea, the anterior and the posterior crista, all areas with numerous Bdnf-beta-galactosidase-positive cells. Few fibers remain to the saccule, utricle, and the base of the cochlea, all areas with few or no Bdnf-beta-galactosidase-positive cells. Thus, retention of fibers is possible with BDNF, even in the absence of differentiated hair cells.

Aging↗
PubMed2005

Smaller inner ear sensory epithelia in Neurog 1 null mice are related to earlier hair cell cycle exit.

We investigated whether co-expression of Neurog 1 and Atoh 1 in common neurosensory precursors could explain the loss of hair cells in Neurog 1 null mice. Analysis of terminal mitosis, using BrdU, supports previous findings regarding timing of exit from cell cycle. Specifically, we show that cell cycle exit occurs in spiral sensory neurons in a base-to-apex progression followed by cell cycle exit of hair cells in the organ of Corti in an apex-to-base progression, with some overlap of cell cycle exit in the apex for both hair cells and spiral sensory neurons. Hair cells in Neurog 1 null mice show cell cycle exit in an apex-to-base progression about 1-2 days earlier. Atoh 1 is expressed in an apex-to-base progression rather then a base-to-apex progression as in wildtype littermates. We tested the possible expression of Atoh1 in neurosensory precursors using two Atoh 1-Cre lines. We show Atoh 1-Cre mediated beta-galactosidase expression in delaminating sensory neuron precursors as well as undifferentiated epithelial cells at E11 and E12.5. PCR analysis shows expression of Atoh 1 in the otocyst as early as E10.5, prior to any histology-based detection techniques. Combined, these data suggest that low levels of Atoh 1 exist much earlier in precursors of hair cells and sensory neurons, possibly including neurosensory precursors. Analysis of Atoh 1-Cre expression in E18.5 embryos and P31 mice reveal beta-galactosidase stain in all hair cells but also in vestibular and cochlear sensory neurons and some supporting cells. A similar expression of Atoh 1-LacZ exists in postnatal and adult vestibular and cochlear sensory neurons, and Atoh 1 expression in vestibular sensory neurons is confirmed with RT-PCR. We propose that the absence of NEUROG 1 protein leads to loss of sensory neuron formation through a phenotypic switch of cycling neurosensory precursors from sensory neuron to hair cell fate. Neurog 1 null mice show a truncation of clonal expansion of hair cell precursors through temporally altered terminal mitosis, thereby resulting in smaller sensory epithelia.

Animals↗
PubMed2005

Normal CFTR Activity and Reversed Skin Potentials in Pseudohypoaldosteronism.

Cystic fibrosis (CF) transmembrane conductance regulator (CFTR) Cl(-) channel function is required for activating amiloride-sensitive epithelial Na(+) channels (ENaC) in salt-absorbing human sweat duct. It is unclear whether ENaC channel function is also required for CFTR activation. The dysfunctional ENaC mutations in type-1 pseudohypoaldosteronism (PHA-1) provided a good opportunity to study this phenomenon of ion channel interaction between CFTR and ENaC. The PHA-1 ducts completely lacked spontaneous ENaC conductance (gENaC). In contrast, the normal ducts showed large spontaneous gENaC (46 +/- 10 ms, mean +/- SE: ). After permeabilization of the basolateral membrane with alpha-toxin, cAMP + ATP activation of CFTR Cl(-) conductance (gCFTR) or alkalinization of cytosolic pH (6.8 to 8.5) stimulated gENaC of normal but not PHA-1 ducts. In contrast, both spontaneous gCFTR in intact ducts and (cAMP + ATP)-activated gCFTR of permeabilized ducts appeared to be similar in normal and PHA-1 subjects. Lack of gENaC completely blocked salt absorption and caused dramatic reversal of skin potentials associated with pilocarpine-induced sweat secretion from significantly negative in normal subjects (-13 +/- 7.0 mV) to significantly positive (+22 +/- 11.0 mV) in PHA-1 patients. We conclude that virtual lack of ENaC in PHA-1 ducts had little effect on CFTR activity and that the positive skin potentials could potentially serve as a diagnostic tool to identify type-1 pseudohypoaldosteronism.

Cystic Fibrosis Transmembrane Conductance Regulato↗
PubMed2005

Job satisfaction of registered dental practitioners.

BACKGROUND: This study was designed to measure job satisfaction among registered clinical dentists so as to identify issues which may influence recruitment and retention of dentists in active clinical practice. METHODS: A questionnaire measuring dimensions of job satisfaction was mailed to a stratified random sample of 80 private and 80 public sector dentists selected from the 1999 Victorian Dental Register. RESULTS: An adjusted response rate of 60 per cent was achieved (n = 87). Analyses showed significant differences (ANOVA; p < 0.05) in levels of satisfaction for various dimensions of job satisfaction by gender, age group and practice type. Differences in job satisfaction between male and female dentists related to the personal time dimension. Differences in satisfaction between dentists of different age groups were attributable to six dimensions: relationships with colleagues, relationships with patients, relationships with staff, personal time, community and administrative responsibilities. Differences between levels of satisfaction among private and public dentists related to the autonomy, relationships with patients, pay and resources dimensions. CONCLUSION: There are various dimensions of job satisfaction that may be pertinent to issues influencing recruitment and retention of dentists. Differences that exist between levels of job satisfaction among private and public sector dentists, between male and female dentists and dentists of different age groups need to be addressed in order to improve recruitment and retention rates of dentists in active clinical practice in different sectors of the dental care system.

Adult↗
PubMed2005

Ancestral RET haplotype associated with Hirschsprung's disease shows linkage disequilibrium breakpoint at -1249.

BACKGROUND: Hirschsprung disease (HSCR) is a complex disorder with traditional germline mutations in RET in up to 30% of familial cases and in 3% of sporadic cases in a population-based series. We have previously demonstrated that an ancestral haplotype at the 5' end of RET (haplotype 0) was strongly associated with a large subset of isolated HSCR cases and that a putative low penetrance susceptibility locus was encompassed within this ancestral haplotype, anchored by exon 2 SNP A45A. OBJECTIVE: To determine the 5' extent of the HSCR-associated ancestral haplotype by defining the linkage disequilibrium breakpoint in search for the low penetrance susceptibility locus. METHODS: Systematic screening of the region upstream of the anchoring A45A SNP, comprising RET intron 1, exon 1, and promoter in 117 population-based HSCR cases and 100 controls. Dual luciferase assay to determine differential activities between SNP combinations near a transcription start site. RESULTS: New SNP's were found which formed upstream haplotypes, anchored by A45A, in linkage disequilibrium with HSCR (2 = 76.96, p<0.00000001). Linkage disequilibrium appeared to break at the -1249C/T SNP. Further, the HSCR-associated genotype (00) was found in >60% of HSCR but only 2% of controls. Because only 2 variants, -200A>G and -196C>A, lie within the promoter region and are in proximity to the transcriptional start site (at -195), we modelled these combinations into constructs for luciferase reporter assay. The HSCR-associated SNP combination showed the lowest activity and the control-associated combination, the highest. CONCLUSIONS: Our observations seem to discard the existence of a HSCR-causing mutation as it is conceived in the traditional sense, but strengthen the idea of a specific combination of variants conferring susceptibility to the disease in a low penetrance fashion. The data derived from our functional "in vitro" studies would suggest that the HSCR-associated haplotype 0 may result in a lower level of expression of the RET gene [corrected]

Case-Control Studies↗
PubMed2005

Aspects of health-related microbiology of the Subin, an urban river in Kumasi, Ghana.

The aim of this study was to assess the influence of urban waste, sewage and other human centred activities on the microbiological quality of the river Subin, which flows through the metropolis of Kumasi, Ghana, and serves as drinking water for communities downstream. Three sites, Racecourse, Asafo and Asago, on the Subin were monitored over a year for total coliforms, faecal coliforms, enterococci and biochemical oxygen demand. Bacterial indicator numbers (geometric mean 100 ml(-1)) varied from 1.61 x 10(9) to 4.06 x 10(13) for total coliforms, 9.75 x 10(8) to 8.98 x 10(12) for faecal coliforms and 1.01 x 10(2) to 6.57 x 10(6) for enterococci. There was a consistent increase in bacterial loading as the river flows from the source (Racecourse) through Kumasi. Bacterial numbers were significantly (p < or = 0.05) higher during the rainy season compared with the dry (harmattan) season. The biochemical oxygen demand ranged from 8 mg l(-1) at the source of the river to 419 mg l(-1) at Asago; none of the sites achieved internationally accepted standards for water quality. The River Subin becomes grossly polluted as it flows through Kumasi and at Asago, a rural community downstream of Kumasi that abstracts water from the river for drinking, this probably contributes to the observed high levels of diarrhoeal disease.

Adolescent↗
PubMed2004

Decay of intestinal enterococci concentrations in high-energy estuarine and coastal waters: towards real-time T90 values for modelling faecal indicators in recreational waters.

Intestinal enterococci are the principal 'health-evidence-based' parameter recommended by WHO for the assessment of marine recreational water compliance. Understanding the survival characteristics of these organisms in nearshore waters is central to public health protection using robust modelling to effect real-time prediction of water quality at recreation sites as recently suggested by WHO and the Commission of the European Communities Previous models have more often focused on the coliform parameters and assumed two static day-time and night-time T90 values to characterise the decay process. The principal driver for enterococci survival is the received dose of irradiance from sunlight. In the water column, transmission of irradiance is determined by turbidity produced by suspended material. This paper reports the results of irradiated microcosm experiments using simulated sunlight to investigate the decay of intestinal enterococci in relatively turbid estuarine and coastal waters collected from the Severn Estuary and Bristol Channel, UK. High-turbidity estuarine waters produced a T90 value of 39.5 h. Low-turbidity coastal waters produced a much shorter T90 value of 6.6 h. In experiments receiving no irradiation, high-turbidity estuarine waters also produced a longer T90 of 65.1 h compared with corresponding low-turbidity coastal waters, T90 24.8 h. Irradiated T90 values were correlated with salinity, turbidity and suspended solids (r>0.8, p<0.001). The results suggest that enterococci decay in irradiated experiments with turbidity >200 NTU is similar to decay observed under dark conditions. Most significantly, these results suggest that modelling turbidity and or suspended solids offers a potential means of predicting T90 values in 'real-time' for discrete cells of a hydrodynamic model.

Dose-Response Relationship, Radiation↗
PubMed2004

Electrophysiological characterization and functional importance of calcium-activated chloride channel in rat uterine myocytes.

In order to better understand the mechanisms underlying excitation of the uterus, we have elucidated the characteristics and functional importance of Ca(2+)-activated Cl(-) currents ( I(Cl-Ca)) in pregnant rat myometrium. In 101/320 freshly isolated myocytes, there was a slowly inactivating tail current (162+/-48 pA) upon repolarization following depolarising steps. This current has a reversal potential close to that for chloride, and was shifted when [Cl(-)] was altered. It was activated by Ca(2+) (but not Ba(2+)) entry through L-type Ca(2+) channels, enhanced by the Ca(2+) channel agonist Bay K8644 (2 microM), and inhibited by the Cl(-) channel blockers, niflumic acid (10 microM) and anthracene-9-carboxylic acid (9-AC, 100 microM). We therefore conclude that the pregnant rat myometrium contains Ca(2+)-activated Cl(-) channels producing inward current in ~30% of its cells. When these channels were inhibited by niflumic acid or 9-AC in intact tissues, the frequency of spontaneous contractions, was significantly reduced. Niflumic acid was also shown to inhibit oxytocin-induced contractions and Ca(2+) transients. Neither 9-AC nor niflumic acid had any effect on high-K-invoked contractions. Taken together these data suggest that Ca(2+)-activated Cl(-) channels are activated by Ca(2+) entry and play a functionally important role in myometrium, probably by contributing to membrane potential and firing frequency (pacemakers) in these cells.

Animals↗
PubMed2004

Attention to single letters activates left extrastriate cortex.

Brain imaging studies examining the component processes of reading using words, non-words, and letter strings frequently report task-related activity in the left extrastriate cortex. Processing of these linguistic materials involves varying degrees of semantic, phonological, and orthographic analysis that are sensitive to individual differences in reading skill and history. In contrast, single letter processing becomes automatized early in life and is not modulated by later linguistic experience to the same degree as are words. In this study, skilled readers attended to different aspects (single letters, symbols, and colors) of an identical stimulus set during separate sessions of functional magnetic resonance imaging (fMRI). Whereas activation in some portions of ventral extrastriate cortex was shared by attention to both alphabetic and non-alphabetic features, a letter-specific area was identified in a portion of left extrastriate cortex (Brodmann's Area 37), lateral to the visual word form area. Our results demonstrate that while minimizing activity related to word-level lexical properties, cortical responses to letter recognition can be isolated from figural and color characteristics of simple stimuli. The practical utility of this finding is discussed in terms of early identification of reading disability.

Adolescent↗
PubMed2004

Which cephalosporin for gonorrhoea?

The recommended treatment for gonorrhoea in the United Kingdom has, until recently, included the fluoroquinolone, ciprofloxacin, which consequently was used by most genitourinary medicine clinics. In 2002 national surveillance data showed that resistance to ciprofloxacin had risen to a prevalence of 9.8% (9% in 2003), indicating that the target of >95% efficacy in first line therapy was no longer achievable. The third generation cephalosporins, ceftriaxone (intramuscular) or cefixime (oral), are the recommended alternatives, but recent audit data reveal other cephalosporins are currently being used to treat gonorrhoea, notably including cefuroxime (intramuscular or, often, oral). A pharmacodynamic analysis was undertaken to determine whether all these regimens were equally potent. Ceftriaxone, 250 (or 500) mg intramuscularly, or cefixime, 400 mg orally, were calculated to give free drug concentrations above the MIC90 for 22-50 hours post dose whereas the cefuroxime regimens being used were pharmacodynamically borderline, achieving this target for only 6.8-11.2 hours and raising the spectre that continued use may select for stepwise increases in resistance, as occurred with penicillin. We therefore underscore that ceftriaxone or cefixime should be the agents of choice to replace ciprofloxacin, as recommended in the new treatment guidelines, and that cefuroxime is a poor substitute.

Anti-Bacterial Agents↗