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D A Dance

Publications and source records attributed to D A Dance.

At least 19 recordsLinked to original sources

The effect of introduction of a guideline on the management of vaginal discharge and in particular bacterial vaginosis in primary care.

BACKGROUND: Bacterial vaginosis (BV) is the commonest cause of vaginal discharge, and its association with obstetric and gynaecological complications is being recognized increasingly. It was our impression that BV was poorly understood and underdiagnosed in family practice. OBJECTIVE: The aim of this study was to explore the management of patients with vaginal symptoms by family practitioners and to see if the management changed after the assimilation of best practice guidelines. METHOD: Family practitioners were invited to complete a baseline questionnaire of their perceived practice, and to record actual practice when consulted about vaginal symptoms, for a minimum of 4 weeks. Consensus best practice guidelines were then provided and practice recorded for a similar period. RESULTS: Baseline data was received from 34 practitioners and suggested that the symptoms and signs of different vaginal infections were not well known. Most symptomatic patients were only investigated at re-presentation with unresolved symptoms or at recurrence, and 43% of respondents treated with empirical antifungals as a first line approach. Pregnant patients were only occasionally asked about symptoms and only occasionally examined if symptomatic. Pre-guideline practice data from 30 practitioners showed 1.2 patient consultations/week, of which 60% were examined and 55% had a high vaginal swab (HVS) sent. Only 2% had near-patient tests done. Post-guideline data from 23 family practitioners showed a lower recorded consultation rate at 0.7/week, but 90% of these were examined, 77% had an HVS sent and 69% had near-patient tests done. Of the 36 HVS examined by Gram stain, 19 (53%) showed Lactobacillus predominant flora and 10 (28%) suggested BV. Seven (19%) were borderline or ungradable. Only three (8%) showed yeasts, one of which also showed BV. CONCLUSIONS: Baseline data supported our impression that BV was under-recognized. Guidelines appeared to improve the rate of investigation of women consulting with vaginal symptoms.

Algorithms↗

Melioidosis as an emerging global problem.

There is remarkably little known about the incidence of melioidosis outside a few countries (Thailand, Australia, Singapore and Malaysia). Presumably it is widespread in tropical south east Asia. Elsewhere there are tantalising glimpses of the tip of what may be a large iceberg. Since a specific diagnosis of melioidosis requires awareness on the part of clinicians, and the existence of a laboratory capable of isolating and identifying Burkholderia pseudomallei, a luxury not available in most rural tropical areas, the size of this iceberg is likely to remain unknown for the foreseeable future. There is mounting evidence that the disease is endemic in the Indian sub-continent and the Caribbean, and there have been unsubstantiated reports of recent cases in South Africa and the Middle East. It is unclear whether melioidosis has really spread to such areas relatively recently, or has been there but unrecognised for a long time. Almost all cases diagnosed in temperate climates have been imported from the tropics, with the exception of a unique outbreak which occurred in France in the mid-1970s. With increasing world wide travel of both humans and other animals, the potential exists for melioidosis to spread to new and fertile pastures.

Burkholderia pseudomallei↗

Ecology of Burkholderia pseudomallei and the interactions between environmental Burkholderia spp. and human-animal hosts.

Early workers thought that melioidosis was a zoonosis with a reservoir in rodents, but we now know that Burkholderia pseudomallei is a widely distributed environmental saprophyte. In northeast Thailand, two thirds of paddy fields yield the organism, and 80% of children have antibodies by the time they are 4 years old. However, interpretation of these results has been complicated by the recent recognition of avirulent, antigenically cross-reacting environmental organisms for which the name B. thailandensis has been proposed. We still know very little about the climatic, physical, chemical and biological factors which control the proliferation and survival of Burkholderia spp. in the environment, although epidemiological studies show space-time clustering of melioidosis. It is assumed that most human and animal melioidosis arises through exposure to contaminated soil or muddy water, although only 6% of human cases have a clear history of inoculation, and a further 0.5% of cases follow near-drowning. Laboratory animals have also been infected by ingestion, inhalation and insect bites, but evidence of infection acquired naturally by these routes remains anecdotal. Sporadic cases have resulted from iatrogenic inoculation, laboratory accidents, and person-to-person or animal-to-person spread. Whether exposure to B. pseudomallei will result in disease probably depends on the balance between the virulence of the strain, the immune status of the host (e.g. diabetes mellitus) and the size of the inoculum.

Animals↗

Molecular phylogeny of Burkholderia pseudomallei.

In terms of population structure, the species Burkholderia pseudomallei contains both clonal and non-clonal elements. By indexing variation in rRNA loci using the restriction endonuclease BamHI, we found that two ribotypes (types 1 and 3) are predominant in nature. Ribotype 3 is prevalent in Asian countries while ribotype 1 is more widespread. Some disease association was suggested for 4 ribotypes and strains of ribotype 4 were markedly associated with a fatal outcome. DNA macrorestriction (XbaI) profiles resolved by pulsed-field gel electrophoresis revealed great heterogeneity within the prevalent ribotypes and these profiles appeared to be reliable strain markers. Arabinose environmental strains were characterised by BamHI ribotypes that were markedly distinct form clinical and environmental isolates of the arabinose negative phenotype.

Bacterial Typing Techniques↗

Serum bactericidal and inhibitory titres in the management of melioidosis.

A retrospective evaluation of the relationship between serum bactericidal and inhibitory titres and treatment outcome in 195 adult Thai patients with severe melioidosis was conducted. Drug regimens included ceftazidime (52% of patients), co-amoxiclav (24%), imipenem (11%) or the conventional four-drug combination (11%). Pre- and 1 h post-dose serum samples were collected after 48-72 h of therapy, and serum inhibitory and bactericidal titrations determined. Median post-dose titres were: bactericidal 1:8 (range 0-1:128) and inhibitory 1:16 (range 0-1:128). Overall mortality was 26% and outcome was not influenced by either inhibitory or bactericidal titres. Pre-dose titres correlated with renal function; renal function was the most important predictor of mortality. Determination of serum inhibitory or bactericidal titres is unhelpful in the management of severe melioidosis.

Adolescent↗

Control of MRSA.

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Humans↗

Urinary tract infection after urodynamic studies in women: incidence and natural history.

OBJECTIVE: To study the incidence, natural history and symptomatic effects of bacteriuria after urodynamic studies in women. PATIENTS AND METHODS: In a prospective study in the urogynaecology clinic of a large District General Hospital, 214 women (mean age 52.3 years, range 23-81) underwent urodynamic studies. Bacteriuria was detected by semiquantitative culture at 2 and 7 days after the test. Women completed a 7-day diary of symptoms and events. RESULTS: The incidence of bacteriuria after urodynamic studies was 7.9%. Bacteriuria was transient in four of 17 women but persisted in nine and developed late in four; only one of 17 infections gave rise to symptoms. Irritative bladder symptoms after the test occurred in 34% of women, but only three went to their doctors because of concern about a possible urinary tract infection. Advancing age was the only variable associated with bacteriuria after urodynamic studies (P= 0.05). Menopausal status, past history of urinary tract infection, number of urethral instrumentations required, order number in a session, peak urinary flow rate and urodynamic diagnosis were not associated variables. CONCLUSIONS: In a large series of women presenting to a urogynaecology clinic, urodynamic investigations were associated with a high incidence of transient irritative symptoms but a low incidence of bacteriuria (8%). Infection was asymptomatic in most patients, but its natural history was unpredictable. Transient, persistent and late cases of bacteriuria all occurred. In this population, urodynamic studies are associated with a low level of morbidity.

Adult↗

Obligatory role of gamma interferon for host survival in a murine model of infection with Burkholderia pseudomallei.

Burkholderia pseudomallei, the causative agent of melioidosis, is a gram-negative bacterium capable of causing either acute lethal sepsis or chronic but eventually fatal disease in infected individuals. However, despite the clinical importance of this infection in areas where it is endemic, there is essentially no information on the mechanisms of protective immunity to the bacterium. We describe here a murine model of either acute or chronic infection with B. pseudomallei in Taylor Outbred (TO) mice which mimics many features of the human pathology. Intraperitoneal infection of TO mice at doses of >10(6) CFU resulted in acute septic shock and death within 2 days. In contrast, at lower doses mice were able to clear the inoculum from the liver and spleen over a 3- to 4-week period, but persistence of the organism at other sites resulted in a chronic infection of between 2 and 16 months duration which was eventually lethal in all of the animals tested. Resistance to acute infection with B. pseudomallei was absolutely dependent upon the production of gamma interferon (IFN-gamma) in vivo. Administration of neutralizing monoclonal antibody against IFN-gamma lowered the 50% lethal dose from >5 x 10(5) to ca. 2 CFU and was associated with 8,500- and 4,400-fold increases in the bacterial burdens in the liver and spleen, respectively, together with extensive destruction of lymphoid architecture in the latter organ within 48 h. Neutralization of either tumor necrosis factor alpha or interleukin-12 but not granulocyte-macrophage colony-stimulating factor, also increased susceptibility to infection in vivo. Together, these results provide the first evidence of a host protective mechanism against B. pseudomallei. The rapid production of IFN-gamma within the first day of infection determines whether the infection proceeds to an acute lethal outcome or becomes chronic.

Acute Disease↗

Stability of strain genotypes of Burkholderia pseudomallei from patients with single and recurrent episodes of melioidosis.

The constancy of strain genotypes of multiple isolates of Burkholderia pseudomallei from 13 patients with melioidosis was examined by BamHI ribotyping and pulsed-field gel electrophoresis (PFGE) of XbaI digests of DNA. Seven of 8 patients with single episodes of melioidosis each yielded genetically identical isolates and only one of five patients with recurrent episodes was infected with a new strain clearly distinct from the original primary strain. Variation was observed in PFGE patterns of primary and relapse isolates of another patient but this was insufficient to define genetically distinct strains. We conclude that most patients with single or multiple episodes of melioidosis retain a single strain.

Burkholderia pseudomallei↗

Effects of Burkholderia pseudomallei and other Burkholderia species on eukaryotic cells in tissue culture.

Burkholderia pseudomallei causes melioidosis, a serious and often fatal bacterial infection. B. pseudomallei can behave as a facultatively intracellular organism and this ability may be important in the pathogenesis of both acute and chronic infection. The uptake of B. pseudomallei and other Burkholderia spp. by cells in tissue culture was examined by electron microscopy. B. pseudomallei can invade cultured cell lines including phagocytic lines such as RAW264, J774 and U937, and non-phagocytic lines such as CaCO-2, Hep2, HeLa, L929, McCoy, Vero and CHO. Uptake was followed by the intracellular multiplication of B. pseudomallei and the induction of cell fusion and multinucleate giant cell formation. Similar effects were produced by B. mallei and B. thailandensis.

Animals↗

An ultrastructural study of the phagocytosis of Burkholderia pseudomallei.

Burkholderia pseudomallei causes melioidosis and is believed to be an intracellular pathogen in human and animal disease. The uptake of B. pseudomallei by mouse peritoneal macrophages and cells in tissue culture was examined by electron microscopy. In all the systems studied B. pseudomallei were phagocytosed and apparently inhibited the normal processes of intracellular killing. Destruction of the phagosome membrane occurred and the bacteria escaped into the cytoplasm.

Animals↗

Factors affecting the pharmacokinetics of parenteral chloramphenicol in enteric fever.

Chloramphenicol pharmacokinetics were studied in 29 Nepalese adults diagnosed with uncomplicated enteric fever and randomized to receive succinate ester 30 mg/kg i.v. or i.m. Serial plasma concentrations of chloramphenicol, and iothalamate (to estimate glomerular filtration rate), antipyrine (hepatocellular function) and Indocyanine Green (liver blood flow) were measured by HPLC and kinetic parameters estimated by non-compartmental analysis. In culture-positive patients (n = 16), mean residence times (MRTs) and steady-state volumes of distribution (V(d)ss) for i.v. chloramphenicol (mean +/- S.D.; 4.9 +/- 0.9 h and 1.9 +/- 0.8 L/kg; n = 7) were less than after i.m. chloramphenicol (12.3 +/- 7.3 h and 3.7 +/- 2.5 L/kg; n = 9; P < 0.05), with a higher peak plasma concentration after i.v. (16.2 +/- 9.1 versus 7.8 +/- 3.6 mg/L; P < 0.05); plasma clearance (Cl(p)) was similar in the two groups (368 +/- 172 and 310 +/- 224 mL/kg/min after i.v. and i.m. respectively). In 17 patients examined during convalescence, MRT and Vdss were less than in acute illness regardless of route chloramphenicol administration. There were similar changes in chloramphenicol kinetic parameters in culture-negative patients. Antipyrine Cl(p) and liver blood flow correlated weakly with chloramphenicol Cl(p) in culture-positive patients (P < 0.1) and were higher in convalescence; no such associations were seen for iothalamate Cl(p). These data indicate that i.v. chloramphenicol produces peak plasma concentrations which are on average twice those after i.m. injection of the same dose, due principally to a smaller V(d)ss. Cl(p) is uninfluenced by route of administration and is determined more by hepatic metabolism than renal excretion. Intramuscular treatment may result in sub-therapeutic chloramphenicol concentrations initially, but continued regular i.v. dosing is more likely to produce levels at which bone marrow toxicity occurs.

Adolescent↗