Methylene blue but not indigo carmine causes DNA damage to colonocytes in vitro and in vivo at concentrations used in clinical chromoendoscopy.
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Cells, Cultured↗
Biomedical subjects
J Davies
Publications and source records attributed to J Davies.
The DNA sequence and biological annotation of human chromosome 1.
The reference sequence for each human chromosome provides the framework for understanding genome function, variation and evolution. Here we report the finished sequence and biological annotation of human chromosome 1. Chromosome 1 is gene-dense, with 3,141 genes and 991 pseudogenes, and many coding sequences overlap. Rearrangements and mutations of chromosome 1 are prevalent in cancer and many other diseases. Patterns of sequence variation reveal signals of recent selection in specific genes that may contribute to human fitness, and also in regions where no function is evident. Fine-scale recombination occurs in hotspots of varying intensity along the sequence, and is enriched near genes. These and other studies of human biology and disease encoded within chromosome 1 are made possible with the highly accurate annotated sequence, as part of the completed set of chromosome sequences that comprise the reference human genome.
Base Sequence↗
Fludarabine phosphate and melphalan: a reduced intensity conditioning regimen suitable for allogeneic transplantation that maintains the graft versus malignancy effect.
Reduced intensity conditioning (RIC) for allogeneic stem cell transplantation allows stable donor cell engraftment with the maintenance of a graft versus malignancy effect. Many different regimens exist employing various combinations of chemotherapy, radiotherapy and T-cell depletion. We examined the role of non-T-cell depleted RIC regimens in 56 patients with haematological malignancies. Patients received fludarabine phosphate for 5 days (30 mg/m2 in 35 patients, 25 mg/m2 in 21 patients) and melphalan for 1 day (140 mg/m2 in 36 patients, 100 mg/m2 in 20 patients). Immunosuppression was with CyA alone in 33 patients and CyA/MTX in 23 patients. Twenty-four of the 26 patients with chimerism data showed >95% donor chimerism at 3 months post transplant. aGVHD occurred in 18% of patients receiving CyA/MTX compared to 53% of patients receiving CyA. The 100-day mortality rate was 0.16 (95%CI 0.08-0.28) and 1-year nonrelapse mortality was 0.24 (95%CI 0.13-0.38). Thirty-three patients remained alive and in CR at a median of 19 months post transplant (range 3-38 months). We have shown that patients transplanted with fludarabine phosphate, melphalan 100 mg/m2 and with CyA/MTX as post transplant immunosuppression can achieve good disease control with an acceptable level of toxicity. Further studies are required to confirm these findings.
Adult↗
Prepregnancy body mass index and dietary intake in the first trimester of pregnancy.
OBJECTIVES: Adequate maternal nutrition is of paramount importance in pregnancy, particularly in the first trimester when fetal development is crucial. It has been reported that heavier women are most likely to fear weight gain associated with pregnancy. Few studies have, however, investigated associations between prepregnancy body mass index (BMI) and nutrient intakes in the first trimester of gestation using detailed, prospective methodologies. The aim of this study was to investigate possible associations between prepregnancy BMI and nutrient intakes in the first trimester of gestation. DESIGN: Seventy-two Caucasian, primiparous nonsmokers of mean age 33.1 years (SD 4.6) were recruited from three London teaching hospitals and they completed a background information questionnaire and a 4- to 7-day weighed inventory food diary during the first trimester of pregnancy. Prepregnancy anthropometric data were extracted from General Practitioner records. RESULTS: Prepregnancy BMI was inversely associated with dietary energy (P = 0.04), Southgate and Englyst fibre (P < 0.01), and iron and folate (P < 0.01). After excluding under-reporters [individual energy intake:basal metabolic rate (estimated) ratio < 1.2], prepregnancy BMI was inversely associated with folate intake (P =0.04). Dietary intakes of Englyst fibre (P = 0.03) were statistically significantly lower than average dietary recommendations in this group. CONCLUSIONS: This study identified that women with a high prepregnancy BMI are more likely to under-report nutrient intakes. The finding that folate intake was significantly lower in heavier women accurately reporting dietary intake is of particular concern.
Adult↗
Success of a nurse led community based genitourinary medicine clinic for young people in Liverpool: review of the first year.
OBJECTIVES: To assess the outcome and workload of a community based, nurse led comprehensive sexual health and contraceptive service for clients aged less than 25. METHODS: Review of appointment diaries and clinic records of clients who attended the Brook genitourinary medicine (GUM) clinic. The workload, case mix, and achievement of national targets in the first year of the service were compared with those for the same age group of clients attending the nearby hospital based GUM clinic. A limited client satisfaction questionnaire was carried out 8 months after the clinic opened. RESULTS: 1061/1700 (62.4%) clients (185, 17.4% male) attended booked appointments. Chlamydia trachomatis was detected in 16.1% of women and 20.5% of men at Brook (p<0.05), where 22.6% of women and 50% of men had at least one sexually transmitted infection (p<0.001). HIV testing was offered to 98.5% of clients. 60.7% of all identified contacts attended a clinic for testing and/or treatment. Client responses to a questionnaire about the service were very favourable. Only 2.3% of Brook GUM clients needed referral to a physician. CONCLUSIONS: Nurse led community based GUM services, such as the one provided at the Merseyside Brook Centre, appeal to young people and our success should encourage others to consider similar ventures.
Adolescent↗
Cystic fibrosis presenting as acute upper airway obstruction.
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Acute Disease↗
Developments in and experience of kilovoltage X-ray cone beam image-guided radiotherapy.
This paper offers a realistic review of kilovoltage X-ray cone beam tomography integrated with the treatment machine for image-guided radiotherapy in the light of experience taking a commercial system from prototype development into clinical use. It shows that key practicalities cannot be ignored, in particular the regular characterization of mechanical flex during gantry rotation, the mapping of defects in flat panel image transducers and their response to X-ray exposure. The number of X-ray projections and the doses required for clinically useful cone beam reconstruction at different therapy sites are considered in the context of imaging that is fit for purpose. Three roles for cone beam tomography in radiotherapy are identified: patient setup in three dimensions (3D), where even low dose cone beam tissue detail is superior to megavoltage imaging; disease targeting where, despite wide field scatter and slow scanning, it is possible to generate images that are suitable for tumour delineation even at challenging sites; adaptive treatment planning, where calibrated cone beam images have been shown to provide sufficient target detail to support "plan of the day" selection and have the potential for planning with bulk corrections. With frequent use in mind, the need to limit patient dose during setup, yet maximize much needed image quality in the target zone, is considered. Finally, it is noted that the development of cone beam tomography for radiotherapy is far from complete, with X-ray source, image transducer, reconstruction algorithms and techniques for image profile collection still being researched.
Humans↗
B-type natriuretic peptide: a simple new test to identify coronary artery disease?
A common key question in clinical medicine is whether coronary artery disease (CAD) is present in a patient. This applies not only to patients with symptomatic chest pain, but also to those at high risk of sudden unexpected death due to asymptomatic CAD, such as diabetics. In both groups of patients, it would be of great benefit if a simple blood test could identify those most likely to have CAD. Such individuals could then be selected for more definitive but more invasive tests for CAD, such as angiography, exercise testing, etc. In addition to its established role in diagnosing heart failure, it appears that BNP may fulfil this function of pre-screening for both symptomatic and asymptomatic CAD. We review the evidence for this new prospect, which has the potential to reduce cardiac deaths by using a simple blood test to better target cardioprotective strategies to those who most need them.
Biomarkers↗
Should parents accompany critically ill children during inter-hospital transport?
BACKGROUND: Parental accompaniment during inter-hospital transportation (retrieval) of critically ill children is not commonplace in the United Kingdom. METHODS: A three month pilot of parental accompaniment was undertaken in 2002 (143 retrievals), after which time the policy was adopted as standard practice. A follow up audit was performed in 2004 (136 retrievals). RESULTS: Findings were remarkably consistent between the two periods. Staff perceived little or no added stress during the majority of transfers (96% in 2002, 98% in 2004), and felt able to perform medical interventions without hindrance (98% in 2002, 100% in 2004). There was good agreement between medical and nursing staff regarding perception of stress and ability to perform interventions (phi statistic 0.57 to 1.00). Adverse events occurred during 11 (3.9%) retrievals; six of these involved a parent exclusively. Stress tended to be associated with adverse events or parental behaviour rather than disease acuity. Staff vetoed the offer of accompaniment on 11 occasions, for a variety of reasons. The majority of parents found the experience safe, beneficial, and perceived a reduction in stress as a result. These data may inform other retrieval services who are considering adopting a similar policy.
Adolescent↗
A marked increase in organ donation in Puerto Rico.
During its first years of existence, the Puerto Rico Transplant Program barely reached 18 to 20 renal transplants per year. A brain death amendment to the law improved the numbers but only to a stable thirty/year. Polls and studies showed that, although people knew about transplantation and expressed willingness to donate, the powerful emotional grief reaction, as well as a peculiar decision-making process, all militated against effective donation. In 1995, LifeLink of Puerto Rico was created as part of the very successful LifeLink Foundation of Tampa, staffed by local professionals. Cadaveric donation increased exponentially by 1227% and in 2004, 22.4 donors per million population were recovered, up from 1.5, one of the steepest growth curves in the United States. As a result, kidney transplantation increased, a cardiac transplant program was inaugurated, a pancreas transplant program has started, and liver will follow. The success is the result of well-trained, culturally sensitive coordinators and requestors; continuous education to the public, hospitals, administrators, neurospecialists, and critical care units; hospital development; implementation of federal law; and a sensitive approach the deceased donor family, and not only to the waiting list patients. The results demonstrate that organizational and educational factors can override cultural obstacles.
Brain Death↗
Salvage cryosurgery for locally recurrent prostate cancer following radiotherapy.
The popularity of radiotherapy as a minimally invasive treatment for prostate cancer is increasing. Despite advancements in radiation delivery, a number of patients will fail treatment. Salvage radical prostatectomy has been the main therapeutic option for locally recurrent radiation failure prostate cancer with curative intent. The operation is technically difficult to perform and associated with significant comorbidities. Salvage cryotherapy has emerged as a minimally invasive alternative option. In this article, we review the role of cryotherapy in recurrent prostate cancer and compare its outcome with salvage radical prostatectomy.
Cryosurgery↗
Screens using RNAi and cDNA expression as surrogates for genetics in mammalian tissue culture cells.
We have developed methods for the automation of transfection-grade DNA preparation, high-throughput retroviral preparation, and highly parallel phenotypic screens to establish approaches that will allow investigators to examine in an unbiased manner the roles of proteins in mammalian cells. These methods have been used to raise or lower the levels of individual kinases in individual micro-well cultures either by cDNA or short hairpin RNA expression and will allow investigators to treat mammalian cells in culture in manners that are analogous to genetic screens in yeast. Our proof-of-principle experiments have been performed in human cells using repositories that represent over 75% of the protein, nucleotide, carbohydrate, lipid, and amino acid kinases in the human genome. These initial experiments have demonstrated the feasibility of two general types of screens. We have performed phenotypic screens to identify proteins with specific roles in a chosen function and genetic interaction screens to establish epistatic relations between different proteins. The results suggest that any phenotype that can be scored by a robust assay in tissue culture is amenable to these types of screens and that interactions between mammalian proteins can be established. These results point to the near-term goal of establishing comprehensive, unbiased screens that will allow queries on the roles of all human proteins.
Carcinoma, Non-Small-Cell Lung↗
'Near-miss' obstruction of a laryngeal mask airway.
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Airway Obstruction↗
Spironolactone reduces brachial pulse wave velocity and PIIINP levels in hypertensive diabetic patients.
AIMS: To assess whether spironolactone has beneficial effects on blood pressure (BP), N-terminal propeptide of type III procollagen (PIIINP) and pulse wave velocity (PWV) in hypertensive, type II diabetics. METHODS: Ten patients with type II diabetes and hypertension were enrolled in a randomized, double-blind crossover study comparing 4 months' treatment with spironolactone and placebo with a 4-week washout phase. BP, PIIINP and carotid-radial PWV were measured at the end of each treatment phase. RESULTS: Compared with placebo, spironolactone reduced systolic BP by 15.6 +/- 46.1 mmHg (P = 0.005, 95% CI 2.7-28.5 mmHg), PIIINP by 0.6 +/- 0.3 microg l(-1) (P = 0.04, 95% CI 0.02-1.1 microg l(-1)) and PWV by 0.6 +/- 0.2 m s(-1) (P = 0.008, 95% CI 0.18-1.02 m s(-1)). CONCLUSIONS: Spironolactone is effective at reducing systolic BP and brachial artery stiffness as indicated by PWV. It also reduces PIIINP in type II diabetic patients with hypertension.
Aged↗
Double-blind randomized controlled study of coblation tonsillotomy versus coblation tonsillectomy on post-operative pain.
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Adolescent↗
An assessment of clinically optimal gold marker length and diameter for pelvic radiotherapy verification using an amorphous silicon flat panel electronic portal imaging device.
Verification of target organ position is essential for the accurate delivery of conformal radiotherapy. Megavoltage electronic portal imaging with flat panel amorphous silicon detectors delivers high quality images that can be used for verification of bony landmark position. Gold markers implanted into the target organ can be visualized and used as a surrogate of actual organ position. On-line compensation for marker displacement, by adjusting patient position, can reduce geometric errors associated with radiation delivery. This study assesses the optimal marker length and diameter to be used with an amorphous silicon (a-Si) flat panel detector and electronic portal images (EPIs), prior to implementation of a clinical programme of gold marker insertion in prostate cancer patients. Seven marker sizes varying from 3 mm to 8 mm in length and 0.8 mm to 1.1 mm in diameter were investigated in a group of patients undergoing pelvic radiotherapy using an 8 MV Elekta SL20 linear accelerator. Markers were placed on the skin entry and exit sites of the treatment beam and EPIs in both lateral and anterior pelvic views were acquired. Three observers independently assessed visibility success and failure using a subjective scoring system. Markers less than 5 mm in length or 0.9 mm in diameter were poorly visualized (<70% visualization success in lateral EPIs). The marker measuring 0.9 mm x 5 mm appears to be clinically optimal in pelvic radiotherapy patients (80% visualization success in lateral EPIs) and will be used for actual organ implantation.
Electronics, Medical↗
Admissibility of scientific evidence in courts.
In its 1993 Daubert v. Merrell Dow opinion, the United States Supreme Court articulated an entirely new set of criteria for the admissibility of scientific expert testimony. In its 1999 Kumho Tire v. Carmichael opinion, the Court extended Daubert's general holding to include non-scientific expert testimony as well. Most modem litigation relies upon the testimony of experts and this testimony can play a dispositive role in litigation. In all parts of the case, liability, causation and damages, lawyers are winning cases by using newly available techniques, suggested by Daubert and Kumho Tire, to exclude the expert testimony that links damages to the act or omission for which their client has been found liable. Our article contains medico-legal analysis of cases, beginning in the application of Israeli case law which discusses the Daubert Court's holding and explaining the scientific principles that the Court cites. The Daubert introduction links to a brief discussion of the Court's 1999 extension of Daubert to non-scientific testimony. We present a two-part model for evaluating the admissibility of scientific evidence--internal and external--in the Israeli courts. The internal examination of the scientific evidence evaluates its reliability by examining the content of the evidence and by checking that its conclusions correspond to the research methods of scientific literature. The court also has to review the abilities and skills of the expert witness. If the evidence passes the internal evaluation, the court will apply an external evaluation by examining whether the scientific evidence coincides with the other evidence presented to the court according to the specific rules of the law applied to the particular case.
Disclosure↗
DNA sequence and analysis of human chromosome 9.
Chromosome 9 is highly structurally polymorphic. It contains the largest autosomal block of heterochromatin, which is heteromorphic in 6-8% of humans, whereas pericentric inversions occur in more than 1% of the population. The finished euchromatic sequence of chromosome 9 comprises 109,044,351 base pairs and represents >99.6% of the region. Analysis of the sequence reveals many intra- and interchromosomal duplications, including segmental duplications adjacent to both the centromere and the large heterochromatic block. We have annotated 1,149 genes, including genes implicated in male-to-female sex reversal, cancer and neurodegenerative disease, and 426 pseudogenes. The chromosome contains the largest interferon gene cluster in the human genome. There is also a region of exceptionally high gene and G + C content including genes paralogous to those in the major histocompatibility complex. We have also detected recently duplicated genes that exhibit different rates of sequence divergence, presumably reflecting natural selection.
Base Composition↗