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Biomedical subjects

M Wills

Publications and source records attributed to M Wills.

At least 19 recordsLinked to original sources
PubMed2005

Do u smoke after txt? Results of a randomised trial of smoking cessation using mobile phone text messaging.

OBJECTIVES: To determine the effectiveness of a mobile phone text messaging smoking cessation programme. DESIGN: Randomised controlled trial SETTING: New Zealand PARTICIPANTS: 1705 smokers from throughout New Zealand who wanted to quit, were aged over 15 years, and owned a mobile phone were randomised to an intervention group that received regular, personalised text messages providing smoking cessation advice, support, and distraction, or to a control group. All participants received a free month of text messaging; starting for the intervention group on their quit day to assist with quitting, and starting for the control group at six months to encourage follow up. Follow up data were available for 1624 (95%) at six weeks and 1265 (74%) at six months. MAIN OUTCOME MEASURES: The main trial outcome was current non-smoking (that is, not smoking in the past week) six weeks after randomisation. Secondary outcomes included current non-smoking at 12 and 26 weeks. RESULTS: More participants had quit at six weeks in the intervention compared to the control group: 239 (28%) v 109 (13%), relative risk 2.20 (95% confidence interval 1.79 to 2.70), p < 0.0001. This treatment effect was consistent across subgroups defined by age, sex, income level, or geographic location (p homogeneity > 0.2). The relative risk estimates were similar in sensitivity analyses adjusting for missing data and salivary cotinine verification tests. Reported quit rates remained high at six months, but there was some uncertainty about between group differences because of incomplete follow up. CONCLUSIONS: This programme offers potential for a new way to help young smokers to quit, being affordable, personalised, age appropriate, and not location dependent. Future research should test these findings in different settings, and provide further assessment of long term quit rates.

Adolescent↗
PubMed2004

Rounded atelectasis in an asbestos exposed worker.

The case history is presented of a 51-year-old electrical power worker with a history of asbestos exposure presenting with rounded atelectasis. No other radiological markers of asbestos exposure were present. A documented history of asbestos exposure and exclusion of other causes of rounded atelectasis led to the diagnosis of asbestos related rounded atelectasis. It is important to understand that rounded atelectasis can be an isolated finding due to asbestos exposure. This facilitates investigation of lung masses of unknown etiology and initiation of appropriate follow up of patients at risk for future development of more debilitating asbestos related pathology.

Asbestos↗
PubMed2001

Palladium-catalyzed tandem reactions to form 1-vinyl-1h-isochromene derivatives.

The palladium-catalyzed reaction of pinacolone with tert-butyldimethyl(3-(2-bromophenyl)allyloxy)silane results in direct formation of 1-vinyl-3-tert-butyl-1H-isochromene. This is the result of a ketone arylation followed by an intramolecular cyclization of the enolate with the allylic system. The use of a lithium diamide base appears to be essential for success. The tert-butyldimethylsilyl protecting group is also an essential choice as it furnishes the appropriate reactivity to promote allylic substitution after the aryl coupling process. The use of more effective leaving groups, such as acetate, results in reaction of the allylic group, and no aryl coupling is observed. Through the appropriate selection of phosphine ligand and solvent, either the cyclized isochromene product or the noncyclized intermediate may be formed selectively. A short combinatorial study of the scope and limitations of the reaction, involving 24 ketones, is described.

Journal Article↗
PubMed2001

Modification and inhibition of vancomycin group antibiotics by formaldehyde and acetaldehyde.

It is shown that several vancomycin group antibiotics (vancomycin, eremomycin, and avoparcin) undergo spontaneous chemical modifications when kept at room temperature at neutral pH in aqueous solutions containing traces of formaldehyde or acetaldehyde. This chemical modification predominantly results in a mass increase of 12 Da in the reaction with formaldehyde and 26 Da in the case of acetaldehyde. By using tandem mass spectrometry the modification can unambiguously be identified as originating from the formation of a ring-closed 4-imidazolidinone moiety at the N-terminus of the glycopeptide antibiotics, that is, near the receptor binding pocket of the glycopeptide antibiotics. Bioaffinity mass spectrometry shows that this ring-closure results in a dramatically decreased affinity for the peptidoglycan-mimicking D-alanyl-D-alanine receptor. Additionally, in vitro inhibition measurements on two different strains of bacteria have revealed that the modified antibiotics display reduced antibacterial activity. The ring-closure is also shown to have a dissociative effect on the dimerization of the vancomycin-analogue eremomycin. The spontaneous reaction of vancomycin with formaldehyde or acetaldehyde may have implications not only for the clinical use of this class of antibiotics, but also for the effectiveness of these antibiotics when they are used in chiral separation chromatography or capillary electrophoresis.

Acetaldehyde↗
PubMed2001

Preliminary results of a randomized controlled trial of prophylactic shock wave lithotripsy for small asymptomatic renal calyceal stones.

OBJECTIVE: To report a prospective, randomized study to determine whether prophylactic extracorporeal shockwave lithotripsy (ESWL) is justified as a treatment for small, asymptomatic calyceal stones. PATIENTS AND METHODS: The study included 228 patients with small (< 15 mm total diameter) asymptomatic calyceal stones; 113 patients were randomized to undergo ESWL and 115 to the control group who were kept under observation. Outcome measurements included the stone-free rate, requirement for additional treatment, symptoms, quality of life and renal function. RESULTS: In all, 200 patients had at least one annual follow-up; all outcome measurements reported were those at the most recent follow-up (mean 2.2 years, range 1-5). In the ESWL group 28 patients (28%) were stone-free, compared with 16 (17%) in the observation group (odds ratio 1.95, 95% confidence interval, CI, 0.97-3.89, P = 0.06). Additional treatment in the form of analgesics, antibiotics, ESWL, stent insertion and ureteroscopy, was required in 21 (21%) patients in the observation group and 15 (15%) in the ESWL group (odds ratio 0.66, 95% CI 0.32-1.37, P = 0.27). Ten patients in the observation group required invasive procedures, vs none in the ESWL group. There was no evidence of differences in the symptoms, quality of life or renal function tests between the arms of the trial at the final follow-up. CONCLUSIONS: Prophylactic ESWL for small asymptomatic renal calyceal stones does not appear to offer any advantage to patients in terms of stone-free rate, quality of life, renal function, symptoms or hospital admissions. However, a policy of observation is associated with a greater risk of requiring more invasive procedures. A longer follow-up is required to assess the validity of these preliminary findings.

Adult↗
PubMed2001

Hand-arm vibration syndrome from exposure to high-pressure hoses.

Hand-arm vibration syndrome has been reported in the literature to occur following exposure to vibration from the use of many tools, but to date there have been no case reports of its occurrence in workers who have used high-pressure hoses, alone or with other tools. To remedy this, the case histories of nine subjects (two without mixed exposure) examined in the UK and Canada are presented, together with their severity classified according to the Stockholm scales. Attention is drawn to the need to use multiple diagnostic tests to establish the diagnosis and the need to implement vibration isolation and damping methodologies, as and when feasible, with respect to hose nozzles in order to minimize the hazard. The ultimate goal for tool manufacturers, hygienists and engineers should be to reduce workplace vibration levels to meet national and international guidelines and legislation, including UK Health & Safety Executive guidelines and European Economic Community directives. The respective risk levels are presented, together with vibration measurements on hoses used by some of the cases.

Canada↗
PubMed2000

Rhodium-Mediated Asymmetric Hydroformylation with a Novel Bis(diazaphospholidine) Ligand We thank the EPSRC for generous funding of this project, and Prof. D. Games and Dr. B. Stein of the EPSRC Mass Spectrometry Service at Swansea for carrying out analyses of certain compounds. We are also very grateful to the Scottish Higher Education Funding Council for funding the Catalyst Evaluation and Optimisation Service (CATS).

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Journal Article↗
PubMed2000

Comparative genomic hybridization analysis of hepatoblastomas.

Prior cytogenetic analyses of hepatoblastomas have shown the most common recurring abnormalities to be trisomy for chromosomes 2 and 20, and a recurrent translocation involving chromosomes 1 and 4 identified in a minority of cases. Four cases have shown double minute chromosomes, which provide cytogenetic evidence for gene amplification, although no particular genes or genetic regions have been shown to be amplified. To further investigate the cytogenetic changes involved in the pathogenesis and progression of hepatoblastoma, this study analyzes 10 tumors by comparative genomic hybridization. Regions of relative gain or loss were found in nine tumors. The most common recurrent abnormalities were gain of the long arm of chromosome 1 (six tumors), gain of chromosomes 2 (seven tumors), 17 (four tumors), and 20 (three tumors), and loss of chromosomes 4 and 11 (two tumors each). Four cases showed restricted regions of high-level gain at 1q32 or 2q24, regions that have previously been reported to be amplified in other tumors, but not in hepatoblastomas. A specific amplified gene has yet to be identified at these loci, although candidate genes have been proposed and may offer targets for future studies. Genes Chromosomes Cancer 27:196-201, 2000.

Child↗
PubMed2000

Chemistry and clinical biology of the bryostatins.

Bryostatins are a class of antineoplastic compounds isolated from the bryozoans Bugula neritina. A wide range of scientific research is currently underway, studying different aspects of the bryostatins. In this review we try to summarize the latest findings, including all the topics involved, from marine biology to medicinal chemistry.

Animals↗
PubMed2000

Early observations of the effect of extracorporeal shockwave lithotripsy on blood pressure: a prospective randomized control clinical trial.

OBJECTIVE: To determine, in a randomized controlled clinical trial, the effect of extracorporeal shock wave lithotripsy (ESWL) on blood pressure. PATIENTS AND METHODS: The trial included 228 patients with small (< 15 mm) asymptomatic calyceal stones who were randomised to undergo ESWL (113 patients) or to an untreated (observed) control group (115 patients). Blood pressure was recorded at randomization using a standardized protocol. Patients undergoing ESWL received a mean (SD) of 5281 (3462) shocks over a mean of 1.75 sessions on one of two lithotripters. Patients were then followed annually, assessing blood pressure and changes in medication. Data were analysed on an intention-to-treat basis. RESULTS: At randomization, 43% of patients in the control group and 53% in the ESWL group were hypertensive. Of the 228 randomized, 200 patients completed at least one annual follow-up, of whom 192 (93 in the control and 99 in the ESWL group) had their blood pressure recorded. The mean follow-up was 2.2 years; 35 (37%) patients in the control and 46 (46%) in the ESWL group were hypertensive (P = 0.19). Seven (7%) patients in the control group and 11 (11%) in the ESWL group were newly diagnosed to be hypertensive (P = 0.35). CONCLUSIONS: In this randomized controlled clinical trial there was no evidence that ESWL causes changes in blood pressure.

Aged↗
PubMed2000

Manipulation of the phenotype of immortalised rat hepatocytes by different culture configurations and by dimethyl sulphoxide.

The liver-specific phenotype of immortalised rat hepatocytes is not irretrievably lost as they age in culture but can be manipulated by modifying the culture environment. Testosterone metabolism was used to investigate the profile of cytochrome P450 isoenzymes present in two immortalised cell lines, P9 and LQC, and in primary cultures of rat hepatocytes, cultured on collagen films, gels and double gel cultures (sandwich configuration). The extent of testosterone metabolism, and the range of metabolites produced, was increased in immortalised cells by the presence of collagen as a substratum film or gel but survival was poorer and the range of metabolites was reduced in sandwich culture. In contrast, testosterone metabolism was retained in primary hepatocytes in sandwich cultures at a higher level than in collagen film or gel cultures. Expression of alpha class glutathione-S-transferases (GSTs) increased and that of GSTP1 decreased (changes which indicate a recovery of normal liver GST phenotype) when the medium of immortalised cell cultures was supplemented with dimethyl sulphoxide (DMSO). DMSO also improved ethoxyresorufin O-deethylation (EROD) and testosterone metabolism in immortalised cells. It also markedly inhibited proliferation, DNA, RNA and protein synthesis. Maximal testosterone metabolism was observed in immortalised cells cultured on collagen gels in the presence of 1% (v/v) DMSO. Development of a protocol for treating immortalised liver cells cultured on collagen gels with DMSO to switch between proliferation and differentiation may provide a convenient system expressing the xenobiotic metabolising enzymes required for in vitro toxicity testing.

Animals↗
PubMed1999

Neural innervation of the newborn exstrophic bladder: an immunohistochemical study.

PURPOSE: Continence in bladder exstrophy is not always easy to attain. Some patients have a small noncontractile bladder while in others an adequate capacity bladder may not contract normally. Innervation of the detrusor determines its ability to contract. The exstrophic bladder during organogenesis does not store urine. Therefore, its requirements for contraction are limited and its innervation would potentially reflect this difference in function. The availability of specific immunostains allows better differentiation of the neural elements in tissue specimens. Our study focuses on myelinated nerves innervating the newborn exstrophic detrusor. MATERIALS AND METHODS: Biopsies were obtained from the anterior wall of 10 newborn exstrophic bladders at the time of initial closure and compared to 10 newborn controls. Patient age at bladder closure ranged from 1 to 90 days (mean 22). Specimens were formalin fixed and paraffin embedded. Then 4 micro. thick sections were stained with S100, an immunostain that stains neural crest elements including Schwann's elements (myelinated nerve fibers). The entire tissue section was examined. Microscopic fields were sequentially examined with a morphometric system comprising a microscope, video camera and personal computer with a video frame grabber. The output image was displayed on a second monitor and the nerves in each field and numbers of fields in each section were counted. To be considered, fields had to have greater than 75% tissue coverage. The average number of nerves per field was compared between the exstrophic bladders and normal controls. RESULTS: The average number of myelinated nerves per field in the newborn exstrophic bladders (0.13 per field) was significantly reduced compared to normal controls (1.25 per field) and statistically significant (p<0.001). This reduction in nerve fibers appeared to be due to lack of smaller fibers with preservation of larger fibers. There was no difference in innervation in cases closed at birth compared to those closed after month 1 of life. CONCLUSIONS: The newborn exstrophic bladder has fewer myelinated nerve fibers than normal controls primarily due to reduction in the smaller fibers which may represent a maturational delay in the development of the exstrophic bladder. Another possible explanation may be degeneration of the fibers due to lack of bladder contraction but no indication of nerve degeneration was evident in our study. Followup studies of patients at various stages of reconstruction will determine the evolution of neural innervation in the exstrophic bladder.

Bladder Exstrophy↗
PubMed1998

Progressive loss of IL-2-expandable HIV-1-specific cytotoxic T lymphocytes during asymptomatic HIV infection.

In HIV-1 infection, circulating HIV-1-specific cytotoxic T lymphocytes (CTL) exist in different states of activation, including activated cytotoxic cells and memory cells. We report that a subpopulation of HIV-1-specific CTL is capable of clonal expansion upon culture with IL-2 without exogenous antigen. The IL-2-expandable HIV-1-specific CTL precursor frequency was reduced in patients with advancing infection, although HIV-1-specific memory CTL could still be detected by stimulation in vitro with allele-specific HIV-1 peptide. Longitudinal analysis during advancing infection showed a progressive decline in the IL-2-expandable HIV-1-specific CTL precursor (CTLp) frequency without a decline in Epstein-Barr virus (EBV)-specific or allo-specific CTLp frequencies. To address mechanisms that may contribute to the decline in the IL-2-expandable HIV-specific CTL response, the requirements for in vitro generation of HIV-1-specific and EBV-specific effector CTL were examined. In the absence of exogenous IL-2 in limiting dilution, generation of EBV-specific CD8+ effector CTL was dependent upon help from CD4+ cells. CD4+ help for EBV-specific CD8+ CTL was observed in asymptomatic HIV infection but not in advanced infection. In the presence of exogenous IL-2, CD4+ cells could also provide help for the optimal generation of HIV-1 peptide-specific CD8+ CTL, because in vitro depletion of CD4+ cells prior to culture using stimulation with an MHC class I-restricted HIV-1 peptide reduced the peptide-specific CD8+ CTL response. We conclude that there is a decline in the IL-2-expandable HIV-1-specific CTL response during advancing infection. There are a number of possible mechanisms for this decline, including a reduction in CD4+ T cell help for in vivo antigen-activated CD8+ T cells.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Impact vibration and hand-arm vibration syndrome.

The case histories of ten workers with Hand-Arm Vibration Syndrome (HAVS) indicate that their predominant vibration exposure was to impact vibration. This association, recognized previously in pedestal grinders and in multiple hand tool users, should now be identified in spot welders and press operators. This will have important implications for compensation claimants as well as prevention development.

Adult↗
PubMed1997

Serum pooling lowers cholesterol recovery.

Matrix effects hinder the transferability of accuracy for cholesterol. A general assumption is that pooled and individual samples yield similar results. We tested the hypothesis that serum-pooling affects the recovery for cholesterol. We pooled 100 serum samples, determining cholesterol of pool and of the individual samples with Hitachi 717 and 914. Over twenty days, we daily determined cholesterol of individual and pooled samples, using a Hitachi 736 and 747 analyzers. For the hundred-sample pool, the pool was 1.1 to 1.5% lower than the individual samples. With the daily pool study, the ratio of 747 to 736 was 1.7% lower for the pooled compared with the individual samples. Therefore, pooling of serum samples causes a decreased recovery, averaging from 1.1-1.7%, and representing 37-57% of the allowable bias for cholesterol (< 3%), and it is thereby significant.

Bias↗
PubMed1995

Highly attenuated HTLV type Ienv poxvirus vaccines induce protection against a cell-associated HTLV type I challenge in rabbits.

The entire envelope protein of the human T cell leukemia/lymphoma virus type I (HTLV-I)1711, obtained from the DNA of a West African healthy HTLV-I-infected patient, was expressed in the highly attenuated poxvirus vaccine vectors ALVAC and NYVAC. These live recombinant vaccine candidates were used to immunize New Zealand White rabbits. Immunization regimens included inoculation of the poxvirus recombinant alone as well as prime/boost protocols using gp63 HTLV-I envelope precursor protein in Alum as the subunit boost. All animals were exposed to an HTLV-I cell-associated challenge (5 x 10(4) cells) from a primary culture of the HTLV-IBOU isolate. The results indicated that two inoculations of the ALVAC-based HTLV-Ienv vaccine candidate protected animals against viral challenge 5 months following the last immunization. However, a combination protocol with ALVAC-env and two additional boosts of gp63 surprisingly failed to confer protection, suggesting that administration of the subunit preparation might be deleterious. Further, in the case of the NYVAC HTLV-Ienv recombinant, protection was afforded as early as 2 months following the first immunization. Last, all the protected animals in the NYVAC and ALVAC trials were challenged 5 months following the initial challenge exposure with 5 ml of blood from an HTLV-IBOU-infected animal, and subsequently became infected. Protection conferred by the attenuated HTLV-Ienv recombinant poxvirus vaccine in the rabbit model might be instrumental for optimizing the immunogenicity of poxvirus-based vaccine candidates against human immunodeficiency virus (HIV), particularly because of the need to enhance protection against cell-to-cell transmission.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

A gene for autosomal dominant nonsyndromic hereditary hearing impairment maps to 4p16.3.

Mapping genes for nonsyndromic hereditary hearing impairment may lead to identification of genes that are essential for the development and preservation of hearing. We studied a family with autosomal dominant, progressive, low frequency sensorineural hearing loss. Linkage analysis employing microsatellite polymorphic markers revealed a fully linked marker (D4S126) at 4p16.3, a gene-rich region containing IT15, the gene for Huntington's disease (HD). For D4S126, the logarithm-of-odds (lod) score was 3.64 at theta = 0, and the overall maximum lod score was 5.05 at theta = 0.05 for D4S412. Analysis of recombinant individuals maps the disease gene to a 1.7 million base pair (Mb) region between D4S412 and D4S432. Genes for two types of mutant mice with abnormal cochleovestibular function, tilted (tlt) and Bronx waltzer (bv), have been mapped to the syntenic region of human 4p16.3 on mouse chromosome 5. Further studies with the goals of cloning a gene for autosomal nonsyndromic hearing impairment and identifying the murine homologue may explain the role of this gene in the development and function of the cochlea.

Adolescent↗