18 research outputs found
A comparison of the interactions of Salmonella Typhi and Salmonella Typhimurium with human monocytes, macrophages and dendritic cells
No full textEThOS - Electronic Theses Online ServiceGBUnited Kingdo
Population pharmacokinetics of artesunate and dihydroartemisinin following intra-rectal dosing of artesunate in malaria patients
No full textBackground: Intra-rectal artesunate has been developed as a potentially life-saving treatment of severe
malaria in rural village settings where administration of parenteral antimalarial drugs is not
possible. We studied the population pharmacokinetics of intra-rectal artesunate and the
relationship with parasitological responses in patients with moderately severe falciparum
malaria.
Methods and Findings: Adults and children in Africa and Southeast Asia with moderately severe malaria were recruited
in two Phase II studies (12 adults from Southeast Asia and 11 children from Africa) with intensive sampling protocols, and three Phase III studies (44 children from Southeast Asia, and 86 children and 26 adults from Africa) with sparse sampling. All patients received 10 mg/kg artesunate as a single intra-rectal dose of suppositories. Venous blood samples were taken during a period of 24h
following dosing. Plasma artesunate and dihydroartemisinin (DHA, the main biologically active metabolite) concentrations were measured by high-performance liquid chromatography with electrochemical detection. The pharmacokinetic properties of DHA were determined using
nonlinear mixed-effects modelling. Artesunate is rapidly hydrolysed in vivo to DHA, and this contributes the majority of antimalarial activity. For DHA, a one-compartment model assuming complete conversion from artesunate and first-order appearance and elimination kinetics gave the best fit to the data. The mean population estimate of apparent clearance (CL/F) was 2.64 (l/kg/
h) with 66% inter-individual variability. The apparent volume of distribution (V/F) was 2.75 (l/kg) with 96% inter-individual variability. The estimated DHA population mean elimination half-life was 43 min. Gender was associated with increased mean CL/F by 1.14 (95% CI: 0.36–1.92) (l/kg/h) for a male compared with a female, and weight was positively associated with V/F. Larger V/Fs were observed for the patients requiring early rescue treatment compared with the remainder, independent of any confounders. No associations between the parasitological responses and the
posterior individual estimates of V/F, CL/F, and AUC0–6h were observed.
Conclusions: The pharmacokinetic properties of DHA were affected only by gender and body weight. Patients with the lowest area under the DHA concentration curve did not have slower parasite clearance, suggesting that rectal artesunate is well absorbed in most patients with moderately
severe malaria. However, a number of modelling assumptions were required due to the large intra- and inter-individual variability of the DHA concentrations
Brucella melitensis prosthetic joint infection in a traveller returning to the UK from Thailand: Case report and review of the literature
No full textSummaryBackgroundBrucella spp. prosthetic joint infections are infrequently reported in the literature, particularly in returning travellers, and optimal treatment is unknown.MethodWe describe a prosthetic joint infection (PJI) caused by Brucella melitensis in a traveller returning to the UK from Thailand, which we believe to be the first detailed report of brucellosis in a traveller returning from this area. The 23 patients with Brucella-related PJI reported in the literature are summarised, together with our case.ResultsThe diagnosis of Brucella-related PJI is difficult to make; only 30% of blood cultures and 75% of joint aspiration cultures were positive in the reported cases. Culture of intraoperative samples provides the best diagnostic yield. In the absence of radiological evidence of joint loosening, combination antimicrobial therapy alone may be appropriate treatment in the first instance; this was successful in 6/7 [86%] of patients, though small numbers of patients and the likelihood of reporting bias warrant caution in drawing any firm conclusions about optimal treatment. Aerosolisation of synovial fluid during joint aspiration procedures and nosocomial infection has been described.ConclusionsBrucella-related PJI should be considered in the differential of travellers returning from endemic areas with PJI, including Thailand. Personal protective equipment including fit tested filtering face piece-3 (FFP3) mask or equivalent is recommended for personnel carrying out joint aspiration when brucellosis is suspected. Travellers can reduce the risk of brucellosis by avoiding unpasteurised dairy products and animal contact (particularly on farms and abattoirs) in endemic areas and should be counselled regarding these risks as part of their pre-travel assessment
A history of the Jewish community of Potchefstroom and environs
No full textIncludes abstract.Includes bibliographical references (leaves 135-141).This study builds on a range of archival sources and traces the history of Potchefstroom Jewry from the mid-nineteenth century to 2008. Beginning with the immigrant experience the processes of assimilation, acculturation and secularization are explored. The Jewish community developed in parallel with the fortunes of the town until external factors prompted the departure of individuals and families to other centres. The inner workings of the communal organizations and the role of functionaries are investigated, as is the individual experience
Investigation, Prevalence and Histology of Colorectal Neoplasia in Patients with Streptococcus Bovis Bacteraemia in a Large Teaching Hospital
No full textTHE SIXTH SERIES IN THE HYDROGEN SPECTRUM
No full textAuthor Institution: National Bureau of StandardsThe first member of the sixth series in the spectrum of atomic hydrogen has been observed in the predicted position at . The source used is a water-cooled discharge tube drawing 640 ma at 5000 volts, this being the maximum energy consumption with the presently available power supply. The tube is fitted with a rocksalt window and exposed end-on. The optimum condition for maintaining an atomic hydrogen discharge as free as possible from the spectrum of is realized by admitting water vapor through a Hopfield leak and pumping continuously. The pressure maintained is the lowest which will permit steady operation of the discharge. Under this condition the current is at maximum and the decrement between successive series the least. A Perkin-Elmer Model 12 spectrometer, with a rocksalt prism, a Hornig thermocouple as furnished with the early models, a Liston-Folb amplifier, and a Speedomax recorder were used in the observations. Reproductions of records, together with those of other hydrogen series, will be displayed. Relative intensities under conditions for maximum development of the series will be discussed
Genetic engineering of Ketogulonigenium vulgare for enhanced production of 2-keto-L-gulonic acid
No full textFolate derivatives are crucial growth factors for Ketogulonigenium vulgare which is used in mixed culture with Bacillus megaterium for the industrial production of 2-keto-L-gulonic acid (2-KGA), the precursor of L-ascorbic acid (L-AA) or vitamin C (Vc). To improve the growth and 2-KGA production, five genes involved in folate biosynthesis identified in a folate gene cluster from Lactococcus lactis MG1363, including folB. folKE, folP, folQ and folC, were over-expressed in K. vulgare. Intracellular folate concentration in the recombinant strain harboring folate biosynthesis genes cluster under the control of P-sdh (sorbose dehydrogenase gene sdh promoter from K. vulgare) was 8 times higher than that of the wildtype K. vulgare DSM 4025 (P<0.001). In shake flask studies, the cell density and 2-KGA production of the recombinant K. vulgare Rif (pMCS2PsdhfolBC) were increased by 18% (P<0.001) and 14% (P<0.001), respectively, under a relatively stable pH 7 condition. In fermentor studies, enhancements around 25% cell density (P<0.001) and approximately 35% 2-KGA productivity (P<0.001) were observed in comparison with the controls without over-expressing the folate biosynthesis genes. This was the first successful study of metabolic engineering on K. vulgare for enhanced 2-KGA production. (C) 2011 Elsevier B.V. All rights reserved.Biotechnology & Applied MicrobiologySCI(E)PubMed5ARTICLE2320-32515
Brucella melitensis prosthetic joint infection in a traveller returning to the UK from Thailand: Case report and review of the literature
No full textBACKGROUNDBrucella spp. prosthetic joint infections are infrequently reported in the literature, particularly in returning travellers, and optimal treatment is unknown.METHODWe describe a prosthetic joint infection (PJI) caused by Brucella melitensis in a traveller returning to the UK from Thailand, which we believe to be the first detailed report of brucellosis in a traveller returning from this area. The 23 patients with Brucella-related PJI reported in the literature are summarised, together with our case.RESULTSThe diagnosis of Brucella-related PJI is difficult to make; only 30% of blood cultures and 75% of joint aspiration cultures were positive in the reported cases. Culture of intraoperative samples provides the best diagnostic yield. In the absence of radiological evidence of joint loosening, combination antimicrobial therapy alone may be appropriate treatment in the first instance; this was successful in 6/7 [86%] of patients, though small numbers of patients and the likelihood of reporting bias warrant caution in drawing any firm conclusions about optimal treatment. Aerosolisation of synovial fluid during joint aspiration procedures and nosocomial infection has been described.CONCLUSIONSBrucella-related PJI should be considered in the differential of travellers returning from endemic areas with PJI, including Thailand. Personal protective equipment including fit tested filtering face piece-3 (FFP3) mask or equivalent is recommended for personnel carrying out joint aspiration when brucellosis is suspected. Travellers can reduce the risk of brucellosis by avoiding unpasteurised dairy products and animal contact (particularly on farms and abattoirs) in endemic areas and should be counselled regarding these risks as part of their pre-travel assessment.</p
Book Reviews
No full textBook Review 1Book Title: Clinical Health Psychology: A Behavioural Medicine PerspectiveBook Author: L. Schlebusch (Ed.)pp. xxii + 366. illustrated. Halfway House: Southern Book Publishers. 1990.Book Review 2Book Title: Human Prenatal DiagnosisBook Authors: K. Filkins & J.F. Russo (Eds.)pp. xvii + 601. Geillustreer. New York: Marcel Dekker. 1990.Book Review 3Book Title: Introduction to Respiratory CareBook Authors: Levitzky, Cairo, Hall (Ed.)Pp. x + 589. Kent: Harcourt, Brace, Jovanovich. 1990.Book Review 4Book Title: Clinical Magnetic Resonance imagingBook Authors: R. R. Edelman, J. R. Hesselink, J. Newhouse & D. J. Sartoris (Eds.)Pp. xx +1192. Illustrated. Kent: Harcourt Brace Jovanovich. 1990Book Review 5Book Title: Basic ToxicologyBook Author: F.C. LuPp. XIV + 361. Illustrated. USA: Hemisphere. 1991Book Review 6Book Title: Controversies in Obstetric Anaesthesia. No. 1Book Author: B. Morgan (Ed.)Pp. vi + 138. Illustrated. Kent: Edward Arnold. 1990.Book Review 7Book Title: Environmental Health Criteria 105: Selected Mycotoxins: Ochratoxins, Trichothecenes, ErgotBook Author: WHOPp. 263. Illustrated. Geneva: WHO. 1990Book Review 8Book Title: Anxiety: Psychobiological and Clinical PerspectivesBook Authors: N. Sartorius, V. Andreoli, G. Cassano, et al. (Eds.)Pp. xv + 292. Illustrated. USA: Hemisphere. 1990Book Review 9Book Title: Current Problems in Epilepsy 7: Focal Epilepsy: Clinical Use of Emission TomographyBook Authors: M. Baldy-Moulinier, N. A. Lassen, J. Engel jun., & S. Askienazy (Eds.)Pp. viii + 216. Illustrated. London: John Libbey & Co. 1990.Book Review 10Book Title: An Otolaryngologist's Guide to AllergyBook Author: H.C. King (Ed.)Pp. xi + 256. Illustrated. Stungan: Georg Thieme Verlag. 1990Book Review 11Book Title: Mainstream Medicine: CardiologyBook Authors: R.G. Charles & A.J. Marshall (Eds.)Pp. ix +449. Illustrated. Durban: Butterworths. 1989.Book Review 12Book Title: Advances if Pineal Research. Vol. 4Book Authors: R.J. Reiter & A Lukaszyk (Eds.)Pp. ix + 278. Illustrated. London: John Libbey & Co. 1990.Book Review 13Book Title: Medico-legal Reportng in Orthopaedic TraumaBook Authors: M.A. Fox & P.S. Fagg (Eds.)Cape Town: Churchill Livinsgtone. 1990.Book Review 14Book Title: Differential Diagnosis in Conventional RadiologyBook Authors: F.A. Burgener & M. Kormano (Eds.)Pp. viii + 866. Illustrated. Stuttgart: Georg Thieme Verlag. 1991.Book Review 15Book Title: Perspectives on Mental Handicap in South AfricaBook Authors: S. Lea & D. Foster (Eds.)Pp. xi + 304. illustrated. Durban: Bunerwonhs. 1990Book Review 16Book Title: Clinical Endocrinology and Metabolism: Water and Salt Homeostasis in Health and DiseaseBook Author: P.H. Bayliss (Ed.)Pp. ix + 578. Illustrated. England: Harcourt Brace Jovanovich. 1989.Book Review 17Book Title: Difficult Medical ManagementBook Author: R.B. Taylor (Ed.)pp. xxvii + 729. illustrated. £47. Kent: Harcourt Brace Jovanovich. 1991Book Review 18Book Title: Introduction to RadiobiologyBook Authors: M. Tubiana, J. Dutreix & A. Wambersie (Eds.) Translated by D.R. Bewley.Pp. 371. Illustrated. London: Taylor & Francis. 1990
Emergence and spread of a human-transmissible multidrug-resistant nontuberculous mycobacterium.
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