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Biomedical subjects

M Williams

Publications and source records attributed to M Williams.

At least 55 records · Page 3Linked to original sources
PubMed2003

Enrichment of gene-coding sequences in maize by genome filtration.

Approximately 80% of the maize genome comprises highly repetitive sequences interspersed with single-copy, gene-rich sequences, and standard genome sequencing strategies are not readily adaptable to this type of genome. Methodologies that enrich for genic sequences might more rapidly generate useful results from complex genomes. Equivalent numbers of clones from maize selected by techniques called methylation filtering and High C0t selection were sequenced to generate approximately 200,000 reads (approximately 132 megabases), which were assembled into contigs. Combination of the two techniques resulted in a sixfold reduction in the effective genome size and a fourfold increase in the gene identification rate in comparison to a nonenriched library.

Chromosomes, Plant↗
PubMed2003

UK Back pain Exercise And Manipulation (UK BEAM) trial--national randomised trial of physical treatments for back pain in primary care: objectives, design and interventions [ISRCTN32683578].

BACKGROUND: Low back pain has major health and social implications. Although there have been many randomised controlled trials of manipulation and exercise for the management of low back pain, the role of these two treatments in its routine management remains unclear. A previous trial comparing private chiropractic treatment with National Health Service (NHS) outpatient treatment, which found a benefit from chiropractic treatment, has been criticised because it did not take treatment location into account. There are data to suggest that general exercise programmes may have beneficial effects on low back pain. The UK Medical Research Council (MRC) has funded this major trial of physical treatments for back pain, based in primary care. It aims to establish if, when added to best care in general practice, a defined package of spinal manipulation and a defined programme of exercise classes (Back to Fitness) improve participant-assessed outcomes. Additionally the trial compares outcomes between participants receiving the spinal manipulation in NHS premises and in private premises. DESIGN: Randomised controlled trial using a 3 x 2 factorial design. METHODS: We sought to randomise 1350 participants with simple low back pain of at least one month's duration. These came from 14 locations across the UK, each with a cluster of 10-15 general practices that were members of the MRC General Practice Research Framework (GPRF). All practices were trained in the active management of low back pain. Participants were randomised to this form of general practice care only, or this general practice care plus manipulation, or this general practice care plus exercise, or this general practice care plus manipulation followed by exercise. Those randomised to manipulation were further randomised to receive treatment in either NHS or private premises. Follow up was by postal questionnaire one, three and 12 months after randomisation. The primary analysis will consider the main treatment effects before interactions between the two treatment packages. Economic analysis will estimate the cost per unit of health utility gained by adding either or both of the treatment packages to general practice care.

Adult↗
PubMed2003

Development of a fluorescent probe for the study of nucleosome assembly and dynamics.

To develop a probe for use in real-time dynamic studies of nucleosomes, core histones (from Drosophila) were conjugated to a DNA-intercalating dye, thiazole orange, by a reaction targeting Cys 110 of histone H3. In the absence of DNA, the conjugated histones are only very weakly fluorescent. However, upon reconstitution into nucleosomes by standard salt dialysis procedures, the probe fluoresces strongly, reflecting its ability to intercalate into the nucleosomal DNA. The probe is also sensitive to the nature of the DNA-histone interaction. Nucleosomes reconstituted by stepwise salt dialysis give a fluorescence signal quite different from that of the species formed when DNA and histones are simply mixed in low salt. In addition, changing either the DNA length or the type of sequence (nucleosome positioning sequences versus random DNA of the same size) used in the reconstitution alters the resulting fluorescence yield. The results are all consistent with the conclusion that a more rigid, less flexible nucleosome structure results in less fluorescence than a looser structure, presumably due to structural constraints on dye intercalation. This probe should be well suited to analyzing nucleosome dynamics and to following factor-mediated assembly and remodeling of nucleosomes in real time, particularly at the single-molecule level.

Animals↗
PubMed2003

Effects of chronic low back pain, age and gender on vertical spinal creep.

This study investigated the effect of chronic low back pain, age, gender, and time of measurement on the magnitude of vertical spinal creep (VSC) and its recovery. A mixed design, involving three independent variables (chronic low back pain, age, and gender) and one repeated variable (time), was used. One hundred and six subjects of both genders, with and without chronic low back pain, aged between 20 and 60 years, participated in the study. The measurement of VSC and its recovery was performed using a seated stadiometer that allowed continuous measurement of VSC without changing the subject's posture over 25 min. Unloaded VSC was measured during the initial 5 min, followed by 10 min with an additional load of 15% of the subject's body weight and then for a further 10 min after the removal of the load. Subjects were grouped into one of eight categories according to the presence of chronic low back pain, age (20-39 years or 40-60 years) and gender. Repeated measures analysis of variance was computed. A significant increase in VSC with time of measurement was observed (p<0.001). No significant main effects for chronic low back pain, age, or gender were found at any time during the 25-min VSC testing protocol. Significant interactions were found between age and gender during the loaded (p=0.02) and unloaded (p=0.02) phases. A significant interaction was found between chronic low back pain and gender at the end of the unloaded phase (p=0.04). These findings suggest a combined influence of chronic low back pain, age, and gender on VSC and its recovery and that the dominance of each variable changed with the time of the measurement. Thus, subjects who differ in the presence of chronic low back pain, age, and gender should not be combined for statistical analysis of VSC and its recovery.

Adult↗
PubMed2003

Lessons learned from raltitrexed--quality assurance, patient education and intensive supportive drugs to optimise tolerability.

Although recent trials have raised concerns about the toxicity of raltitrexed monotherapy in patients with advanced colorectal cancer (aCRC), similar concerns have also been raised with other chemotherapy regimens in aCRC. The lessons learnt form our previous experiences with raltitrexed are, therefore, still important as they offer practical guidances to optimise tolerability of chemotherapy for CRC in general. The aims of the study were to report the low-toxicity profile in 58 patients receiving raltitrexed when a rigorous patient information and education strategy was implemented together with an intensive supportive adjuvant drugs regimen from the start. After a discussion with the consultant, all patients received a further consultation with a specialist nurse, a series of bespoke information tools, including an information video and written guidelines on how to avoid, prevent and deal promptly with the side-effects of raltitrexed. They all received intravenous adjuvant ondansetron and dexamethasone, then oral domperidone, ranitidine and nystatin from cycle one. The dose intensity was 98% over 307 cycles. Toxicity associated with raltitrexed comprised grade 1/2 diarrhoea (31.6% of treatment cycles), nausea (12.4%) and vomiting (8.4%), with no grade 3/4 events; grade 1/2 alopecia (17.9%); grade 1 (only) stomatitis (2.3%) and grade 1/2/3 lethargy (70.3%, only 2.3% grade 3), anaemia (14.3%, only 0.3% grade 3) and neutropenia (3.3%, only 0.3% grade 3). There were no treatment-related deaths. The low toxicity, despite high-dose intensity, suggests that intensive supportive education and drugs should have a role in the future design of regimens containing raltitrexed and other chemotherapy regimens for colorectal carcinoma.

Adult↗
PubMed2003

Presentation of diaphragmatic herniae during pregnancy and labour.

We report two cases of pregnancy-related diaphragmatic hernia. Case one was a 36-year-old woman who presented in her ninth pregnancy, after eight vaginal deliveries. Eight months after a stab wound to the chest, she developed persistent vomiting. The diagnosis was made by chest X-ray after a contralateral central line had been inserted for parenteral nutrition. A 6 x 4 cm stab-induce defect in the diaphragm was repaired. Close by was a second healed diaphragmatic stab wound. Case two involved a 32-year-old woman with a history of repaired childhood diaphragmatic hernia. She developed atypical shoulder and precordial chest pain during labour. Delivery was achieved by the vaginal route, ventouse-assisted. Persistent pain and vomiting led to insertion of a nasogastric tube and the diagnosis was made on the subsequent chest X-ray. The omentum was very adherent to the lung and could only be mobilised via a thoracotomy, at which significant air leaks occurred but settled rapidly. The difficulties of diagnosis are discussed along with the embryology, mechanisms and management of this condition.

Journal Article↗
PubMed2003

The effect of a nutritional source of tryptophan on dieting-induced changes in brain 5-HT function.

BACKGROUND: Dieting in healthy women results in a decrease in the availability of tryptophan (TRP), the amino-acid precursor of serotonin (5-HT), for brain 5-HT synthesis. This is associated with increases in the prolactin response to 5-HT drug challenge suggesting a 'supersensitivity' of 5-HT neuroendocrine responses. The aim of the study was to assess whether increased TRP intake during dieting would prevent the changes in TRP availability and 5-HT neuroendocrine function. METHOD: Fifty female subjects underwent a 1000 kcal daily diet for 3 weeks. In the final week of the diet subjects were randomly allocated to receive either nutritionally-sourced TRP (1.8 g daily) or placebo in a double-blind, parallel group, design. RESULTS: TRP supplementation failed to modify the dieting-induced reduction in fasting TRP availability to the brain. However, in contrast to placebo-treated subjects, subjects receiving additional TRP did not show enhanced prolactin responses to intravenous TRP challenge. CONCLUSIONS: The decrease in TRP availability produced by dieting may be due to increased TRP metabolism rather than decreased TRP intake. While TRP treatment did not increase fasting TRP availability it may have modified the effect of dieting on brain 5-HT function. Further studies will be needed to see if this effect of TRP has consequences for the effectiveness of dieting as means of weight control.

Administration, Oral↗
PubMed2003

False positive Kleihauer tests and unnecessary administration of anti-D immunoglobulin.

This obstetric case shows two false negative Kleihauer tests and two persistently positive Kleihauer tests leading to unnecessary administration of anti-D immunoglobulin. A diagnosis of hereditary persistence foetal haemoglobin (HPFH) was only confirmed by access to flow cytometry making use of both anti-HbF and anti-D labels. The case highlights the importance of a high index of clinical suspicion for HPFH and the importance of access to flow cytometry estimation of minor RhD red cell populations postnatally in RhD-negative mothers.

Adult↗
PubMed2003

Acute myelogenous leukemia complicated by acute necrotizing ulcerative gingivitis due to Aspergillus terreus.

Infections caused by Aspergillus terreus are rare but have been associated with a poor outcome in immunocompromised patients due to frequent resistance to conventional antifungal therapy. This report describes a case of a woman who developed acute necrotizing ulcerative gingivitis (ANUG) due to A. terreus during induction chemotherapy for acute myelogenous leukemia. She initially failed to respond to treatment with amphotericin B but the infection resolved following the introduction of oral itraconazole. Opportunistic infections caused by A. terreus are an emerging problem and can be associated with a high mortality rate. Early microbiological diagnosis is critical since resistance to amphotericin B is likely and itraconazole appears to be an effective treatment for this infection.

Adolescent↗
PubMed2003

[MRI of the ear].

The purpose of this review article is to describe the normal anatomy, the specific imaging techniques and the applications of MR imaging to temporal bone pathologies. Though the evaluation of the ear is mainly based upon CT, MR imaging is essential in the work-up of tumors and inflammatory diseases, such as epidermoids, cholesterol granulomas, paragangliomas and transtegmental masses. MR Imaging is mandatory in the evaluation of the internal acoustic canal and the cerebellopontine angle. Finally, MR imaging plays an important role in the detection of recurrent cholesteatoma after middle ear surgery, and in the work-up of the labyrinthic cavities before cochlear implantation.

Ear Diseases↗
PubMed2002

Design of high essential amino acid proteins: two design strategies for improving protease resistance of the nutritious MB-1 protein.

Protein design is currently used for the creation of new proteins with desirable traits. In our lab, we focus on the synthesis of proteins with high essential amino acid content having potential applications in animal nutrition. One of the limitations we face in this endeavour is achieving stable proteins despite a highly biased amino acid content. We report here the synthesis and characterisation of two mutants derived from our MB-1 designer protein. The first mutant contains a disulphide bridge designed to cross-link remote segments of the polypeptide chain. The second one is a Tyr62-Trp mutant, where position 62 is buried in the core of the protein. Both mutants were found to be largely helical as per design, and based on thermal denaturation experiments, were substantially more stable than the MB-1 parent molecule. Enhancement of conformational stability in MB-1Trp translated into an impressive improvement of its ability to resist proteolytic degradation. Furthermore, digestion experiments intended to model degradation of proteins in a cow's rumen revealed that MB-1Trp's resistance to degradation compared to that of cytochrome c. Design strategies used for these mutants are discussed with regards to their applicability in creating efficient nutritional proteins.

Amino Acid Sequence↗
PubMed2002

Reliability of the vertical spinal creep response measured in sitting (asymptomatic and low-back pain subjects).

Vertical spinal creep (or change in stature) has been used as an index of spinal loading, yet reliability of the testing protocol has not been fully examined. This study investigated the reliability of a vertical spinal creep response in 10 asymptomatic and five low-back pain subjects. Each subject performed the 25-min testing protocol, which consisted of three phases (5-min preload, 10-min loaded and 10-min unloaded), at the same time on two separate days. Good reliabilities in vertical spinal creep response between two days of testing were demonstrated for both asymptomatic and low-back pain subjects.

Adult↗
PubMed2002

Use of inverse PCR to amplify and sequence breakpoints of HPRT deletion and translocation mutations.

Deletion and translocation mutations have been shown to play a significant role in the genesis of many cancers. The hprt gene located at Xq26 is a frequently used marker gene in human mutational studies. In an attempt to better understand potential mutational mechanisms involved in deletions and translocations, inverse PCR (IPCR) methods to amplify and sequence the breakpoints of hprt mutants classified as translocations and large deletions were developed. IPCR involves the digestion of DNA with a restriction enzyme, circularization of the fragments produced, and PCR amplification around the circle with primers oriented in a direction opposite to that of conventional PCR. The use of this technique allows amplification into an unknown region, in this case through the hprt breakpoint into the unknown joined sequence. Through the use of this procedure, two translocation, one inversion, and two external deletion hprt breakpoint sequences were isolated and sequenced. The isolated IPCR products range in size from 0.4 to 1.8 kb, and were amplified from circles ranging in size from 0.6 to 7.7 kb. We have shown that inverse PCR is useful to sequence translocation and large deletion mutant breakpoints in the hprt gene.

Base Sequence↗
PubMed2002

A review of intensity modulated radiation therapy: incorporating a report on the seventh education workshop of the ACPSEM--ACT/NSW branch. Australasian College of Physical Scientists and Engineers in Medicine.

Intensity modulated radiation therapy (IMRT) is an evolving treatment technique that has become a clinical treatment option in several radiotherapy centres around the world. In August 2001 the ACT/NSW branch of the ACPSEM held its seventh education workshop, the subject was IMRT. This review considers the current use of IMRT and reports on the proceedings of the workshop. The workshop provided some of the theory behind IMRT, discussion of the practical issues associated with IMRT, and also involved presentations from Australian centres that had clinically implemented IMRT. The main topics of discussion were patient selection, plan assessment, multi-disciplinary approach, quality assurance and delivery of IMRT. Key points that were emphasised were the need for a balanced multi-disciplinary approach to IMRT, in both the establishment and maintenance of an IMRT program; the importance of the accuracy of the final dose distribution as compared to the minor in-field fluctuations of individual beams; and that IMRT is an emerging treatment technique, undergoing continuing development and refinement.

Australian Capital Territory↗
PubMed2002

Lower prevalence of pre-morbid neurological illness in African-Caribbean than White psychotic patients in England.

BACKGROUND: It has been suggested that the increased incidence of psychosis in African-Caribbeans living in England may be due to illnesses in which social stress plays an important aetiological role. If this is the case, the prevalence of factors associated with psychosis that predate illness onset such as obstetric complications, pre-morbid neurological illness and poor childhood social adjustment may be expected to be lower in African-Caribbean than Whites psychotic patients. METHOD: Details of obstetric complications, pre-morbid neurological illness, and pre-morbid social adjustment were obtained for 337 psychotic patients by patient interview, interviews of mothers and chart review. The proportions of patients with each 'risk factor' in the African-Caribbean (N = 103) and White (N = 184) groups were compared using regression analysis; age, sex, social class, diagnosis and referral status were possible explanatory variables. RESULTS: African-Caribbean patients were less likely to have suffered a pre-morbid neurological disorder than their White counterparts (odds ratio 0.19, 95% CI 0.06-0.61). There was no significant difference in pre-morbid social adjustment or obstetric complications between the two groups, though fewer obstetric complications were reported in the African-Caribbean group (21.5%) than the White group (30.9%). CONCLUSIONS: African-Caribbean patients with psychosis have experienced less pre-morbid neurological illness.

Black or African American↗
PubMed2002

Fatty acid, amino acid, and trace mineral analyses of five weaning foods from Jos, Nigeria.

Five plant-based weaning foods (WF) (Dietrend, Jot-M, Soy, Ang, and Vic-T) locally prepared in Jos, Nigeria were analyzed by gas-liquid chromatography, reverse-phase high performance liquid chromatography, and atomic emission spectrometry with inductively coupled plasma to determine their fatty acid (FA), amino acid, and trace mineral contents, respectively. Results of these direct analyses were compared to expected values derived from food composition tables prepared by the United States Department of Agriculture (USDA). Additionally, results were compared against recommended nutrient values, using breast milk as the standard for FA content and recommended dietary allowances (RDA) for amino acid and mineral contents. The overall nutritional value of the five WF varied considerably and the quantities of particular nutrients determined by direct analysis differed markedly from those estimated using USDA food tables. Comparison of WF fatty acid composition relative to the RDA recommendations and a human milk standard revealed a much higher proportion of both linoleic (35-55 wt%) and alpha-linolenic acids (1%-7 wt%) relative to human milk lipids (11%-12% and 0.8%-0.9% wt, respectively); however, the WF were devoid of arachidonic acid and docosahexaenoic acid. Soy contained the highest amounts of linoleic acid (59.7 mg/g) and alpha-linolenic acid (7.46 mg/g) compared to the other four WF (10.2-41.0 and 0.35-3.18 mg/g, respectively). The linoleic acid/alpha-linolenic acid ratio was within the recommended range (5:1 to 10:1) in only Jot-M (10:1) and Soy (8:1). Dietrend, Vic-T and Ang, contained linoleic/alpha-linolenic ratios of 12:1, 29:1, and 82:1, respectively. The Soy weaning food would provide the most protein (24.3 g/day), based on an estimated daily intake of 65 g of weaning food by a normal six-month-old infant, compared to Jot-M (11.9 g/day), Dietrend (11.7 g/day), Ang (8.07 g/day), and Vic-T (7.26 g/day). The protein RDA for children up to 1 year of age is 13-14 g/day. Comparison of the mineral contents of the WF to the RDAs for various minerals indicated that all five would provide suboptimal amounts of calcium (16 to 250 mg/day) and zinc (1.42 to 3.56 mg/day) compared to respective RDAs of 400 mg/day and 5 mg/day. These data show that the Soy weaning food is an excellent source of linoleic acid and alpha-linolenic acid, as well as being a good source of high quality protein. Jot-M and Dietrend provide useful amounts of the essential FA; however, it is advisable to reevaluate the composition of Ang and Vic-T to find ways to improve the linoleic/alpha-linolenic ratio of each and increase their total protein content. These results document the shortcomings of using published food composition tables based on foods in America when devising weaning foods based on ingredients in another part of the world.

Amino Acids↗