Publications by authors named "R Keira Cheetham"

59 Publications

Somatic genetic alterations in synchronous and metachronous low-grade serous tumours and high-grade carcinomas of the adnexa.

Histopathology 2019 Mar 15;74(4):638-650. Epub 2019 Jan 15.

Department of Pathology, Belfast Health and Social Care Trust, Belfast, UK.

Aims: Low-grade serous carcinomas (LGSCs) and their precursors serous borderline tumours (SBTs) characteristically harbour mutations in BRAF, KRAS or NRAS but rarely in TP53, whereas high-grade serous carcinomas (HGSCs) are characterised by frequent TP53 mutations but rare BRAF, KRAS or NRAS mutations. In a small subset of cases, LGSCs and/or SBTs develop into high-grade tumours, including HGSCs and poorly differentiated carcinomas (PDCs). Here, we sought to define the repertoire of somatic genetic alterations in low-grade serous tumours and synchronous or metachronous high-grade adnexal carcinomas.

Methods And Results: DNA extracted from five SBTs/LGSCs and synchronous or metachronous HGSCs/PDCs and matched normal tissue was subjected to massively parallel sequencing targeting all exons and selected non-coding regions of 341 cancer-related genes. The low-grade and high-grade tumours from a given case were related, and shared mutations and copy number alterations. Progression from low-grade to high-grade lesions was observed, and involved the acquisition of additional mutations and/or copy number alterations, or shifts from subclonal to clonal mutations. Only two (an HGSC and a PDC) of the five high-grade tumours investigated harboured TP53 mutations, whereas NRAS and KRAS hotspot mutations were seen in two HGSCs and one HGSC, respectively.

Conclusions: Our results suggest that progression from SBT to HGSC may take place in a subset of cases, and that at least some of the rare HGSCs lacking TP53 mutations may be derived from a low-grade serous precursor.
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http://dx.doi.org/10.1111/his.13796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6626549PMC
March 2019

Prevalence and characteristics of multi-modal hallucinations in people with psychosis who experience visual hallucinations.

Psychiatry Res 2018 11 13;269:25-30. Epub 2018 Aug 13.

School of Psychology, Newcastle University, Newcastle upon Tyne, United Kingdom; Older People's Psychology Service, Northumberland, Tyne and Wear NHS Foundation Trust, Bensham Hospital, Gateshead, United Kingdom.

Hallucinations can occur in single or multiple sensory modalities. Historically, greater attention has been paid to single sensory modality experiences with a comparative neglect of hallucinations that occur across two or more sensory modalities (multi-modal hallucinations). With growing evidence suggesting that visual hallucinations may be experienced along with other hallucinations, this study aimed to explore multi-modal hallucinations in a sample of people with psychotic disorders who reported visual hallucinations (n = 22). No participants reported just visual hallucinations i.e. all reported related or unrelated auditory hallucinations. Twenty-one participants reported multi-modal hallucinations that were serial in nature, whereby they saw visual hallucinations and heard unrelated auditory hallucinations at other times. Nineteen people out of the twenty two also reported simultaneous multi-modal hallucinations, with the most common being an image that talked to and touched them. Multi-modal related and simultaneous hallucinations appeared to be associated with greater conviction that the experiences were real, and greater distress. Theoretical and clinical implications of multi-modal hallucinations are discussed.
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http://dx.doi.org/10.1016/j.psychres.2018.08.032DOI Listing
November 2018

Genomic Hallmarks and Structural Variation in Metastatic Prostate Cancer.

Cell 2018 07 19;174(3):758-769.e9. Epub 2018 Jul 19.

Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco (UCSF), San Francisco, CA, USA; Division of Hematology and Oncology, Department of Medicine, UCSF, San Francisco, CA, USA; Department of Radiation Oncology, UCSF, San Francisco, CA, USA; Department of Urology, UCSF, San Francisco, CA, USA. Electronic address:

While mutations affecting protein-coding regions have been examined across many cancers, structural variants at the genome-wide level are still poorly defined. Through integrative deep whole-genome and -transcriptome analysis of 101 castration-resistant prostate cancer metastases (109X tumor/38X normal coverage), we identified structural variants altering critical regulators of tumorigenesis and progression not detectable by exome approaches. Notably, we observed amplification of an intergenic enhancer region 624 kb upstream of the androgen receptor (AR) in 81% of patients, correlating with increased AR expression. Tandem duplication hotspots also occur near MYC, in lncRNAs associated with post-translational MYC regulation. Classes of structural variations were linked to distinct DNA repair deficiencies, suggesting their etiology, including associations of CDK12 mutation with tandem duplications, TP53 inactivation with inverted rearrangements and chromothripsis, and BRCA2 inactivation with deletions. Together, these observations provide a comprehensive view of how structural variations affect critical regulators in metastatic prostate cancer.
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http://dx.doi.org/10.1016/j.cell.2018.06.039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6425931PMC
July 2018

The experience of captaincy in professional sport: The case of elite professional rugby.

Eur J Sport Sci 2017 Mar 1;17(2):215-221. Epub 2016 Nov 1.

a Department of Sport and Exercise , University of Winchester , Winchester , UK.

The captain is perceived to be an important member of the leadership structure within teams across many professional sports. However, while there is a general acceptance that this is the case, there is very little research exploring the role and associated demands at an elite level. As a result, the aim of this study was to explore the captaincy experiences of elite professional rugby union captains. The participants were eight male captains purposefully sampled for this study. Participants were interviewed individually to gain an understanding of each participant's captaincy experiences. The data were thematically analysed using interpretative phenomenological analysis. Nine super-ordinate themes emerged in the study: role, skills, requirements, challenges, the coach, development, experience, context, and approach. Results suggest that the captaincy role is broader than previously highlighted, particularly at the elite level. Also, the study highlights inconsistencies in the selection of captains and a lack of formal developmental support for elite rugby captains. As a result, future research should explore the development of specific evidence-based approaches to captain selection and development.
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http://dx.doi.org/10.1080/17461391.2016.1245788DOI Listing
March 2017

Whole-genome sequencing provides new insights into the clonal architecture of Barrett's esophagus and esophageal adenocarcinoma.

Nat Genet 2015 Sep 20;47(9):1038-1046. Epub 2015 Jul 20.

Medical Research Council Cancer Unit, Hutchison/Medical Research Council Research Centre, University of Cambridge, Cambridge, UK.

The molecular genetic relationship between esophageal adenocarcinoma (EAC) and its precursor lesion, Barrett's esophagus, is poorly understood. Using whole-genome sequencing on 23 paired Barrett's esophagus and EAC samples, together with one in-depth Barrett's esophagus case study sampled over time and space, we have provided the following new insights: (i) Barrett's esophagus is polyclonal and highly mutated even in the absence of dysplasia; (ii) when cancer develops, copy number increases and heterogeneity persists such that the spectrum of mutations often shows surprisingly little overlap between EAC and adjacent Barrett's esophagus; and (iii) despite differences in specific coding mutations, the mutational context suggests a common causative insult underlying these two conditions. From a clinical perspective, the histopathological assessment of dysplasia appears to be a poor reflection of the molecular disarray within the Barrett's epithelium, and a molecular Cytosponge technique overcomes sampling bias and has the capacity to reflect the entire clonal architecture.
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http://dx.doi.org/10.1038/ng.3357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4556068PMC
September 2015

TP53 mutations, tetraploidy and homologous recombination repair defects in early stage high-grade serous ovarian cancer.

Nucleic Acids Res 2015 Aug 27;43(14):6945-58. Epub 2015 Apr 27.

Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA.

To determine early somatic changes in high-grade serous ovarian cancer (HGSOC), we performed whole genome sequencing on a rare collection of 16 low stage HGSOCs. The majority showed extensive structural alterations (one had an ultramutated profile), exhibited high levels of p53 immunoreactivity, and harboured a TP53 mutation, deletion or inactivation. BRCA1 and BRCA2 mutations were observed in two tumors, with nine showing evidence of a homologous recombination (HR) defect. Combined Analysis with The Cancer Genome Atlas (TCGA) indicated that low and late stage HGSOCs have similar mutation and copy number profiles. We also found evidence that deleterious TP53 mutations are the earliest events, followed by deletions or loss of heterozygosity (LOH) of chromosomes carrying TP53, BRCA1 or BRCA2. Inactivation of HR appears to be an early event, as 62.5% of tumours showed a LOH pattern suggestive of HR defects. Three tumours with the highest ploidy had little genome-wide LOH, yet one of these had a homozygous somatic frame-shift BRCA2 mutation, suggesting that some carcinomas begin as tetraploid then descend into diploidy accompanied by genome-wide LOH. Lastly, we found evidence that structural variants (SV) cluster in HGSOC, but are absent in one ultramutated tumor, providing insights into the pathogenesis of low stage HGSOC.
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http://dx.doi.org/10.1093/nar/gkv111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4538798PMC
August 2015

APOBEC3B upregulation and genomic mutation patterns in serous ovarian carcinoma.

Cancer Res 2013 Dec 23;73(24):7222-31. Epub 2013 Oct 23.

Authors' Affiliations: Biochemistry, Molecular Biology and Biophysics Department; Masonic Cancer Center, University of Minnesota, Minneapolis; Division of Biomedical Statistics and Informatics, Department of Health Sciences Research; Medical Genome Facility and Department of Laboratory Medicine and Pathology; Department of Laboratory Medicine and Pathology; Division of Medical Oncology, Department of Oncology; Division of Epidemiology, Department of Health Sciences Research; Division of Oncology Research, Department of Oncology; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic; Women's Cancer Program, Mayo Clinic Cancer Center, Rochester, Minnesota; Department of Cancer Biology, University of Kansas, Kansas City, Kansas; Department of Obstetrics & Gynecology, University of Washington School of Medicine, Seattle, Washington; and Illumina Cambridge Ltd, Chesterford Research Park, Little Chesterford, Cambridge, United Kingdom.

Ovarian cancer is a clinically and molecularly heterogeneous disease. The driving forces behind this variability are unknown. Here, we report wide variation in the expression of the DNA cytosine deaminase APOBEC3B, with elevated expression in the majority of ovarian cancer cell lines (three SDs above the mean of normal ovarian surface epithelial cells) and high-grade primary ovarian cancers. APOBEC3B is active in the nucleus of several ovarian cancer cell lines and elicits a biochemical preference for deamination of cytosines in 5'-TC dinucleotides. Importantly, examination of whole-genome sequence from 16 ovarian cancers reveals that APOBEC3B expression correlates with total mutation load as well as elevated levels of transversion mutations. In particular, high APOBEC3B expression correlates with C-to-A and C-to-G transversion mutations within 5'-TC dinucleotide motifs in early-stage high-grade serous ovarian cancer genomes, suggesting that APOBEC3B-catalyzed genomic uracil lesions are further processed by downstream DNA "repair" enzymes including error-prone translesion polymerases. These data identify a potential role for APOBEC3B in serous ovarian cancer genomic instability.
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http://dx.doi.org/10.1158/0008-5472.CAN-13-1753DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3867573PMC
December 2013

Strelka: accurate somatic small-variant calling from sequenced tumor-normal sample pairs.

Bioinformatics 2012 Jul 10;28(14):1811-7. Epub 2012 May 10.

Illumina, Inc., 5200 Illumina Way, San Diego, CA 92122, USA.

Motivation: Whole genome and exome sequencing of matched tumor-normal sample pairs is becoming routine in cancer research. The consequent increased demand for somatic variant analysis of paired samples requires methods specialized to model this problem so as to sensitively call variants at any practical level of tumor impurity.

Results: We describe Strelka, a method for somatic SNV and small indel detection from sequencing data of matched tumor-normal samples. The method uses a novel Bayesian approach which represents continuous allele frequencies for both tumor and normal samples, while leveraging the expected genotype structure of the normal. This is achieved by representing the normal sample as a mixture of germline variation with noise, and representing the tumor sample as a mixture of the normal sample with somatic variation. A natural consequence of the model structure is that sensitivity can be maintained at high tumor impurity without requiring purity estimates. We demonstrate that the method has superior accuracy and sensitivity on impure samples compared with approaches based on either diploid genotype likelihoods or general allele-frequency tests.

Availability: The Strelka workflow source code is available at ftp://strelka@ftp.illumina.com/.

Contact: csaunders@illumina.com
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http://dx.doi.org/10.1093/bioinformatics/bts271DOI Listing
July 2012

Genome sequencing and analysis of the Tasmanian devil and its transmissible cancer.

Cell 2012 Feb;148(4):780-91

Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, UK.

The Tasmanian devil (Sarcophilus harrisii), the largest marsupial carnivore, is endangered due to a transmissible facial cancer spread by direct transfer of living cancer cells through biting. Here we describe the sequencing, assembly, and annotation of the Tasmanian devil genome and whole-genome sequences for two geographically distant subclones of the cancer. Genomic analysis suggests that the cancer first arose from a female Tasmanian devil and that the clone has subsequently genetically diverged during its spread across Tasmania. The devil cancer genome contains more than 17,000 somatic base substitution mutations and bears the imprint of a distinct mutational process. Genotyping of somatic mutations in 104 geographically and temporally distributed Tasmanian devil tumors reveals the pattern of evolution and spread of this parasitic clonal lineage, with evidence of a selective sweep in one geographical area and persistence of parallel lineages in other populations.
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http://dx.doi.org/10.1016/j.cell.2011.11.065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3281993PMC
February 2012

Mapping copy number variation by population-scale genome sequencing.

Nature 2011 Feb;470(7332):59-65

Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Genomic structural variants (SVs) are abundant in humans, differing from other forms of variation in extent, origin and functional impact. Despite progress in SV characterization, the nucleotide resolution architecture of most SVs remains unknown. We constructed a map of unbalanced SVs (that is, copy number variants) based on whole genome DNA sequencing data from 185 human genomes, integrating evidence from complementary SV discovery approaches with extensive experimental validations. Our map encompassed 22,025 deletions and 6,000 additional SVs, including insertions and tandem duplications. Most SVs (53%) were mapped to nucleotide resolution, which facilitated analysing their origin and functional impact. We examined numerous whole and partial gene deletions with a genotyping approach and observed a depletion of gene disruptions amongst high frequency deletions. Furthermore, we observed differences in the size spectra of SVs originating from distinct formation mechanisms, and constructed a map of SV hotspots formed by common mechanisms. Our analytical framework and SV map serves as a resource for sequencing-based association studies.
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http://dx.doi.org/10.1038/nature09708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3077050PMC
February 2011

CNAseg--a novel framework for identification of copy number changes in cancer from second-generation sequencing data.

Bioinformatics 2010 Dec 21;26(24):3051-8. Epub 2010 Oct 21.

Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Cambridge, UK.

Motivation: Copy number abnormalities (CNAs) represent an important type of genetic mutation that can lead to abnormal cell growth and proliferation. New high-throughput sequencing technologies promise comprehensive characterization of CNAs. In contrast to microarrays, where probe design follows a carefully developed protocol, reads represent a random sample from a library and may be prone to representation biases due to GC content and other factors. The discrimination between true and false positive CNAs becomes an important issue.

Results: We present a novel approach, called CNAseg, to identify CNAs from second-generation sequencing data. It uses depth of coverage to estimate copy number states and flowcell-to-flowcell variability in cancer and normal samples to control the false positive rate. We tested the method using the COLO-829 melanoma cell line sequenced to 40-fold coverage. An extensive simulation scheme was developed to recreate different scenarios of copy number changes and depth of coverage by altering a real dataset with spiked-in CNAs. Comparison to alternative approaches using both real and simulated datasets showed that CNAseg achieves superior precision and improved sensitivity estimates.

Availability: The CNAseg package and test data are available at http://www.compbio.group.cam.ac.uk/software.html.
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http://dx.doi.org/10.1093/bioinformatics/btq587DOI Listing
December 2010

A comprehensive catalogue of somatic mutations from a human cancer genome.

Nature 2010 Jan 16;463(7278):191-6. Epub 2009 Dec 16.

Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK.

All cancers carry somatic mutations. A subset of these somatic alterations, termed driver mutations, confer selective growth advantage and are implicated in cancer development, whereas the remainder are passengers. Here we have sequenced the genomes of a malignant melanoma and a lymphoblastoid cell line from the same person, providing the first comprehensive catalogue of somatic mutations from an individual cancer. The catalogue provides remarkable insights into the forces that have shaped this cancer genome. The dominant mutational signature reflects DNA damage due to ultraviolet light exposure, a known risk factor for malignant melanoma, whereas the uneven distribution of mutations across the genome, with a lower prevalence in gene footprints, indicates that DNA repair has been preferentially deployed towards transcribed regions. The results illustrate the power of a cancer genome sequence to reveal traces of the DNA damage, repair, mutation and selection processes that were operative years before the cancer became symptomatic.
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http://dx.doi.org/10.1038/nature08658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3145108PMC
January 2010

Genomic diversity among drug sensitive and multidrug resistant isolates of Mycobacterium tuberculosis with identical DNA fingerprints.

PLoS One 2009 Oct 12;4(10):e7407. Epub 2009 Oct 12.

Molecular Mycobacteriology, Research Center Borstel, Borstel, Germany.

Background: Mycobacterium tuberculosis complex (MTBC), the causative agent of tuberculosis (TB), is characterized by low sequence diversity making this bacterium one of the classical examples of a genetically monomorphic pathogen. Because of this limited DNA sequence variation, routine genotyping of clinical MTBC isolates for epidemiological purposes relies on highly discriminatory DNA fingerprinting methods based on mobile and repetitive genetic elements. According to the standard view, isolates exhibiting the same fingerprinting pattern are considered direct progeny of the same bacterial clone, and most likely reflect ongoing transmission or disease relapse within individual patients.

Methodology/principal Findings: Here we further investigated this assumption and used massively parallel whole-genome sequencing to compare one drug-susceptible (K-1) and one multidrug resistant (MDR) isolate (K-2) of a rapidly spreading M. tuberculosis Beijing genotype clone from a high incidence region (Karakalpakstan, Uzbekistan). Both isolates shared the same IS6110 RFLP pattern and the same allele at 23 out of 24 MIRU-VNTR loci. We generated 23.9 million (K-1) and 33.0 million (K-2) paired 50 bp purity filtered reads corresponding to a mean coverage of 483.5 fold and 656.1 fold respectively. Compared with the laboratory strain H37Rv both Beijing isolates shared 1,209 SNPs. The two Beijing isolates differed by 130 SNPs and one large deletion. The susceptible isolate had 55 specific SNPs, while the MDR variant had 75 specific SNPs, including the five known resistance-conferring mutations.

Conclusions: Our results suggest that M. tuberculosis isolates exhibiting identical DNA fingerprinting patterns can harbour substantial genomic diversity. Because this heterogeneity is not captured by traditional genotyping of MTBC, some aspects of the transmission dynamics of tuberculosis could be missed or misinterpreted. Furthermore, a valid differentiation between disease relapse and exogenous reinfection might be impossible using standard genotyping tools if the overall diversity of circulating clones is limited. These findings have important implications for clinical trials of new anti-tuberculosis drugs.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0007407PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2756628PMC
October 2009

Bacillus subtilis FZB24 affects flower quantity and quality of saffron (Crocus sativus).

Planta Med 2008 Aug 11;74(10):1316-20. Epub 2008 Jul 11.

Medicinal and Aromatic Plants Dept., National Research Centre (NRC), Cairo, Egypt.

The effect of Bacillus subtilis FZB24 on saffron ( Crocus sativus L.) was studied using saffron corms from Spain and the powdered form of B. SUBTILIS FZB24(R). Corms were soaked in water or in B. subtilis FZB24 spore solution for 15 min before sowing. Some corms were further soil drenched with the spore solution 6, 10 or 14 weeks after sowing. Growth and saffron stigma chemical composition were measured. Compared to untreated controls, application of B. subtilis FZB24 significantly increased leaf length, flowers per corm, weight of the first flower stigma, total stigma biomass; microbe addition also significantly decreased the time required for corms to sprout and the number of shoot sprouts. Compared to the controls, picrocrocin, crocetin and safranal compounds were significantly increased when the plants were soil drenched with the spore solution 14 weeks after sowing; in contrast crocin was highest in untreated controls. Results of this study suggest that application of B. subtilis FZB24 may provide some benefit to saffron growers by speeding corm growth (earlier shoot emergence) and increasing stigma biomass yield by 12 %. While some treatment conditions also increased saffron chemical composition, these were generally not the same treatments that simultaneously improved growth yields and thus, more study is required.
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http://dx.doi.org/10.1055/s-2008-1081293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3947403PMC
August 2008

The use of electronic mail in biomedical communication.

J Am Med Inform Assoc 2000 Jan-Feb;7(1):103-5

Department of Medicine, University of Liverpool, University Hospital Aintree, United Kingdom.

Objectives: To determine whether there are statistically significant differences in the content of electronic mail (e-mail) and conventional mail sent to authors of papers published in medical journals.

Design: Prospective study by postal questionnaire. Over two one-month periods, corresponding authors of papers published in medical journals were asked to record details of the correspondence prompted by their publications.

Measurements: Conventional and e-mail correspondence received. Reprint requests. Content of correspondence. Quality of correspondence.

Results: Eighty-two of 96 authors replied. Fifty received e-mail (mean, 5.7+/-8.8 e-mails per author) and 72 received conventional mail (15.5+/-32.8 letters per author) (p < 0.05). Seventy percent of e-mails and only 53% of correspondence sent by conventional mail (p < 0.05) referred to the content of the paper.

Conclusions: Publication in general medical journals stimulates more conventional than electronic mail. However, the content of e-mail may be of greater scientific relevance. Electronic mail can be encouraged without fear of diminishing the quality of the communications received.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC61459PMC
http://dx.doi.org/10.1136/jamia.2000.0070103DOI Listing
March 2000

A comparison of mebendazole and albendazole in treating children with Trichuris trichiura infection in Durban, South Africa.

S Afr Med J 1998 Jul;88(7):880-3

Medical Research Council, Durban.

Objective: To compare the efficacy of mebendazole 500 mg and albendazole 400 mg single-dose treatments of Trichuris trichiura infection in children in the Durban area of KwaZuluNatal, South Africa.

Design: A single-blind randomised trial in children with a documented moderate infection of T. trichiura. Ova were counted in stool specimens before and 10 days after treatment by the formal-ether concentration method.

Setting: Two shelters for abandoned and orphaned children in Durban.

Participants: Ninety-six children aged between 2 and 12 years.

Outcome Measures: The number of children who showed reduced T. trichiura ova counts after the treatments, and reductions in ova counts, both expressed as percentages. Statistical analysis using the Wilcoxon 2-sample test and the chi-square test.

Results: Eighty-two children completed the trial; 42 received mebendazole and 40 albendazole. Of the mebendazole group 85% showed a reduction in T. trichiura ova count, compared with 75% of children who received albendazole. Mebendazole treatment was associated with a median percentage reduction in ova count of 72.2%, which significantly exceeded the 44.1% reduction after albendazole (P = 0.024).

Conclusion: The mebendazole 500 mg single-dose therapy was more efficacious than the albendazole 400 mg single-dose therapy in treating T. trichiura infection in these children.
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July 1998

Cryopreservation of transformed (hairy) roots of Artemisia annua.

Cryobiology 1996 Feb;33(1):106-17

Department of Biology and Biotechnology, Worcester Polytechnic Institute, Worcester, Massachusetts, 01609, USA.

The antimalarial drug artemisinin has been found in transformed (hairy) roots of Artemisia annua. A protocol was developed to preserve A. annua hairy roots in liquid nitrogen. Root tips were excised from 7-day-old cultures and held on solid White's medium for 24 h prior to cryoprotection. They were then treated with a cryoprotecting mixture containing 8% (v/v) dimethyl sulfoxide (Me2SO) and 20% (w/v) sucrose at 25 degrees C for 1 h followed by cooling at 0.09 degrees C/min to 4 degrees C then cooling to -35 degrees C at 0.72 degrees C/min. Vials containing the root tips were then plunged into liquid nitrogen. After thawing in a water bath to 37 degrees C, root tips were held in the cryoprotecting mixture for 10 min before it was diluted to 25% of its original concentration. Root tips were washed once with fresh liquid White's medium and held for 1 h prior to culturing on White's medium with 0.2% Gelrite and 3% (w/v) sucrose. Regrowth of root tips averaged 65%. Independent variables in this study included 1) Me2SO concentration; 2) the type and concentration of cosolutes; 3) cooling rate(s); 4) the temperature at which the sample is transferred to liquid nitrogen; 5) the age of the culture from which root tips are taken; 6) the recovery period between root tip excision and immersion in cryoprotectant; and 7) the amount of Gelrite used in the postthaw plating medium.
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http://dx.doi.org/10.1006/cryo.1996.0011DOI Listing
February 1996

Light inhibits the formation of capsaicin from capsicum callus.

Planta Med 1992 Jun;58(3):278-9

Worcester Polytechnic Institute, Worcester, MA, 01609. U.S.A.

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http://dx.doi.org/10.1055/s-2006-961455DOI Listing
June 1992

Drug treatment of experimental Capillaria hepatica infection in mice.

Parasitol Res 1991 ;77(6):517-20

Department of Zoology, University of Witwatersrand, Johannesburg, South Africa.

This report presents the results obtained using 14 anthelmintic compounds that were tested in experimental white mice of the Swiss-Webster strain for their action against Capilaria hepatica. Four of the drugs effectively prevented deposition of C. hepatica ova in mouse liver. The doses at which these four drugs prevented greater than 99% of egg deposition were: albendazole, 30 mg/kg; febantel, 30 mg/kg; mebendazole, 3.13 mg/kg; and oxfendazole, 12.5 mg/kg. Of these, mebendazole is the only agent for which the application of five daily doses of 3.13 mg/kg lay within the dose range recommended for man.
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http://dx.doi.org/10.1007/BF00928420DOI Listing
November 1991

The highlights, and the lows, of aviation medicine in the 1940's: the human element.

Authors:
R W Cheetham

Aviat Space Environ Med 1989 Jul;60(7):706-10

University of Natal, Umhlanga Rocks, Republic of South Africa.

This article describes the experience and knowledge gained by the author during an extensive study tour of the majority of aviation medicine centres in the United Kingdom, Canada, and the United States in 1942. The emphasis is upon the human element rather than the technical, and the contribution of thousands of scientists from medical, psychological, and allied disciplines whose dedication was vital to air supremacy. This required a symbiosis between them and aircraft engineers and, inter alia, courageous participation in operational missions or dangerous experiments. The price was, on occasion, tragedy. Individual instances are described, as are visits to operational air force squadrons. The tour concluded with a return to South Africa and the establishment of the first South African Aviation Medical Laboratory. In spite of the implementation of the knowledge gained during the tour, the laboratory was closed after the war.
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July 1989

Novel method for studying the public health significance of macroinvertebrates occurring in potable water.

Appl Environ Microbiol 1984 May;47(5):889-94

An experimental procedure was developed to study the association of selected bacteria and macroinvertebrates and their response to free available chlorine disinfection. The organisms selected for study were Escherichia coli ( LacZ545 ), Enterobacter cloacae (ATCC 23355), and the amphipod Hyalella azteca . E. coli was shown to bind tightly (1.6 X 10(4) CFU per amphipod ) to this macroinvertebrate and to resist repeated attempts to wash it off. E. cloacae was shown to bind much less tightly (1.4 X 10(3) CFU per amphipod ) to H. azteca and was less resistant to removal by washing. The extent of association is a function of macroinvertebrate size (surface area), but the procedure produces repeatable results usable for controlled experimentation. This method, together with the dual bacterial identification criteria (morphology and antibiotic resistance), was used to study the response of unassociated and associated E. coli and E. cloacae to disinfection with free available chlorine at 1.0 mg/liter. Unassociated E. coli populations decreased to less than 1% of their zero time controls within 1 min of contact time, whereas more than 2% of the associated E. coli populations remained viable after 60 min of contact at 1.0 mg of free available chlorine per liter. Unassociated E. cloacae populations decreased to less than 1% of their zero time controls within 1 min of contact time, whereas ca. 15% of the associated E. cloacae populations remained viable after 60 min of contact at 1.0 mg of free available chlorine per liter.(ABSTRACT TRUNCATED AT 250 WORDS)
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC240006PMC
http://dx.doi.org/10.1128/AEM.47.5.889-894.1984DOI Listing
May 1984

A potent new dipeptide inhibitor of cell sickling and haemoglobin S gelation.

Eur J Biochem 1983 Oct;136(1):209-14

A dipeptide L-lysine-L-phenylalanine is shown to inhibit both cell sickling and the gelation of solutions of sickle-cell haemoglobin. The effect on deoxyhaemoglobin solutions and gels was followed by centrifugation; a progressive inhibition of gelation was observed up to 30 mM Lys-Phe. The haemoglobin concentration at the plateau (26 g/dl) suggests that an effect might be seen in vivo if suitable concentrations of Lys-Phe (about 20 mM) can be maintained in the blood stream. Additional studies of lag time before onset of gelation support this. Oxygen dissociation curves of sickle cells showed an effect of Lys-Phe only after incubation for 3 h before measurement, the P50 decreasing from 51 mmHg (6.8 MPa) to 41 mmHg (5.5 MPa) for cells depleted of 2,3-bisphosphoglycerate. The effect of Lys-Phe on intact sickle cells was more rapid. A marked increase in the number of unsickled cells in the presence of Lys-Phe was observed after only 15 min incubation. This result, together with measurements of uptake both into the cell and onto the cell membrane shows that the compound produces a membrane-mediated antisickling effect in addition to the effect on haemoglobin in solution within the cell. The membrane effect is not due to a change in cell volume. The properties of this dipeptide may be of value in the treatment of impending and early sickle crisis.
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http://dx.doi.org/10.1111/j.1432-1033.1983.tb07728.xDOI Listing
October 1983

The sexing of bloodstains by testosterone: total protein ratio determination.

Forensic Sci Int 1983 Aug-Sep;22(2-3):195-201

A simple method for the extraction of testosterone from bloodstains followed by its measurement by radioimmunoassay is described. Complete discrimination of males and females was achieved with measured bloodstains as small as 40 microliters. With stains of unknown volume the total protein content of the stain was determined as an internal reference level. Using the testosterone/protein ratio unequivocal identification was possible for 75% of the stains from males and 50% from females.
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http://dx.doi.org/10.1016/0379-0738(83)90014-2DOI Listing
January 1984

The sexing of bloodstains by testosterone: total protein ratio determination.

Forensic Sci Int 1983 Aug-Sep;22(2-3):195-201

A simple method for the extraction of testosterone from bloodstains followed by its measurement by radioimmunoassay is described. Complete discrimination of males and females was achieved with measured bloodstains as small as 40 microliters. With stains of unknown volume the total protein content of the stain was determined as an internal reference level. Using the testosterone/protein ratio unequivocal identification was possible for 75% of the stains from males and 50% from females.
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http://dx.doi.org/10.1016/0379-0738(83)90014-2DOI Listing
January 1984

Priests before healers--an appraisal of the iSangoma or iSanusi in Nguni society.

S Afr Med J 1982 Dec;62(25):959-60

The total role of the iSangoma or iSanusi within the Nguni culture in Africa is discussed. The importance of the religious and social functions and divinatory powers are emphasized in an endeavour to determined the bases for the therapeutic capacities associated with the so-called 'traditional healer'.
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December 1982

Sickness and medicine--an African paradigm.

S Afr Med J 1982 Dec;62(25):954-6

The concepts of sickness employed in the practice of Western medicine and those held by the Nguni peoples in Africa are shown to be disparate. The approach of the so-called 'traditional healer' incorporates the world-view of the culture within which she works, and her ministrations are consonant with the prevailing beliefs of the community. It is therefore postulated that within this context the application of conventional Western therapeutic techniques can be inappropriate and consequently ineffective.
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December 1982

The traditional healer/diviner as psychotherapist.

S Afr Med J 1982 Dec;62(25):957-8

Appreciation of the apparent efficacy of the traditional healer/diviner in the alleviation of psychological disturbances led to an examination of his/her methods and training in comparison to those of the Western psychotherapist. Models of the themes, components and effects of psychotherapy can be seen to be applicable in both instances, although the functions and roles of healers and psychotherapists in their respective societies may differ. The implications of these analyses as regards the enhancement of the effects of therapeutic intervention are examined.
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December 1982

Psychiatric disorders of the puerperium in South African women of Nguni origin. A pilot study.

S Afr Med J 1981 Sep;60(13):502-6

The clinical impression gained from symptoms exhibited by Zulu and Xhosa obstetric patients referred to the Department of Psychiatry, King Edward VIII Hospital, Durban, was that certain of the psychiatric disorders presented in a different form to those observed in hospitals serving other population groups. Opinions differ as to the aetiology and relationship of disorders of the puerperium to other psychiatric syndromes with controversial hypotheses referring to both the aetiology and the symptomatology. Firstly, the disorders are considered to be a reaction to specific psychological or biological stresses of pregnancy. Secondly, in contradistinction, it is postulated that the illness is incidental to ongoing personality disintegration, which is manifested by premorbid personality disturbances, a family history of mental illness, a past history of psychiatric disorder and nonspecific stresses common to all other psychiatric illnesses. This pilot study indicates that cultural phenomena contributed to the symptoms of the majority of the 31 severely disturbed Black women displaying psychiatric features in the puerperium studies. While confirming the findings of a number of other authors, we have also detected a high incidence of transient situational disturbances of short duration. The findings indicate the need for more detailed research in this area among Black patients.
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September 1981

Psychiatric disorders of the puerperium in South African women of Nguni origin. A pilot study.

S Afr Med J 1981 Sep;60(13):502-6

The clinical impression gained from symptoms exhibited by Zulu and Xhosa obstetric patients referred to the Department of Psychiatry, King Edward VIII Hospital, Durban, was that certain of the psychiatric disorders presented in a different form to those observed in hospitals serving other population groups. Opinions differ as to the aetiology and relationship of disorders of the puerperium to other psychiatric syndromes with controversial hypotheses referring to both the aetiology and the symptomatology. Firstly, the disorders are considered to be a reaction to specific psychological or biological stresses of pregnancy. Secondly, in contradistinction, it is postulated that the illness is incidental to ongoing personality disintegration, which is manifested by premorbid personality disturbances, a family history of mental illness, a past history of psychiatric disorder and nonspecific stresses common to all other psychiatric illnesses. This pilot study indicates that cultural phenomena contributed to the symptoms of the majority of the 31 severely disturbed Black women displaying psychiatric features in the puerperium studies. While confirming the findings of a number of other authors, we have also detected a high incidence of transient situational disturbances of short duration. The findings indicate the need for more detailed research in this area among Black patients.
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September 1981