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Biomedical subjects

P White

Publications and source records attributed to P White.

At least 37 records · Page 2Linked to original sources
PubMed2002

Reviews of acupuncture for chronic neck pain: pitfalls in conducting systematic reviews.

This paper examines some of the problems specifically associated with conducting research into acupuncture and how this can lead to further problems with subsequent systematic reviews. Studies for the treatment of chronic neck pain have been used as examples of how presented information can be misleading to an acupuncture-naive reader and how researchers must be sensitive to these problems when compiling their inclusion and exclusion criteria. The problems associated with scoring trials are discussed and further work to increase the scope of scoring mechanisms is recommended in order to produce meaningful systematic reviews in the future.

Acupuncture Therapy↗
PubMed2002

A fourth case of 8p11 myeloproliferative disorder transforming to B-lineage acute lymphoblastic leukaemia. A case report.

A 56-year-old male presented with inguinal lymphadenopathy and leucocytosis (WBC 98 x 10(9)/l). Bone marrow morphology showed myeloid hyperplasia, with eosinophilia. Cytogenetic analysis showed no evidence of the Philadelphia chromosome, and fluorescence in situ hybridisation studies for the BCR/ABL fusion were negative. All cells examined showed the t(8;13)(p11;q12) translocation. Six weeks after presentation, the disease progressed to an acute lymphoblastic leukaemia (ALL). The lymphoblasts were CD19/CD10 dual positive. Cytogenetic analysis again showed the t(8;13) translocation, with no additional abnormalities. There have been at least 14 reported cases of the t(8;13) myeloproliferative disorder to date, of which only 3 transformed to B-lineage ALL: our case is the 4th.

Bone Marrow Cells↗
PubMed2002

Legal issues in teleradiology-distant thoughts!

Advancements in computer technology and telecommunications have meant that all diagnostic images can now be acquired as digital signals, however the ethicolegal concepts surrounding this innovation remain unclear. In the UK there are limited practice guidelines on legal issues relating specifically to telemedicine or teleradiology. It is not yet clear whether the current law relates to telemedicine in the same way that it does for other medical specialties, or whether telemedicine raises new legal issues that need clarification. This article attempts to outline some of the potential legal issues, but the absence of case law and legislation in this area will ensure that many questions remain unanswered. The legal implications of teleradiology/telemedicine are addressed, and literature, laws and professional guidelines from the UK, USA, Australia and New Zealand are reviewed, focusing on the American licensure laws, professional relationships with patients with regards to liability, responsibility, accountability and duty of care issues, as well as issues of missed diagnosis, misdiagnosis, security and confidentiality. Teleradiology, while being actively practised worldwide, gives rise to many unanswered medicolegal questions. It is suggested that guidelines need to be implemented to safeguard patients and professionals alike.

Australia↗
PubMed2002

Mobilization of calcium in glasshouse tomato plants by localized scorching.

It is postulated here that significant amounts of calcium will be mobilized into the plant by the scorching of one old leaf. This postulate was tested using large (6 m) tomato plants in the glasshouse. Brief scorching with a blowlamp was shown to release some 35% of the leaf's water into the plant. A range of measurements was used to estimate the kinetics and magnitude of this flow. The flow was found to carry a pulse of up to 50% of the leaf's total calcium into the plant, probably via the xylem, and was estimated to increase xylem calcium levels transiently by a factor of about 80. The potential value of scorching treatments in combating calcium-deficiency disorders is discussed.

Adaptation, Physiological↗
PubMed2001

Identification of poor prognostic features among patients requiring mechanical ventilation after hematopoietic stem cell transplantation.

Patients who develop respiratory failure requiring mechanical ventilation after hematopoietic stem cell transplantation (HSCT) have very high mortality. Several investigators have identified prognostic features that can be used to identify a subset of these patients who are virtually certain to die, yet these have never been prospectively assessed. The objectives of this study were to determine the accuracy of published prognostic features for mortality and to determine the survival of patients who recover from respiratory failure. A systematic review of the literature was undertaken to identify reported poor prognostic features and survival rates. The study validated the reported poor prognostic features on a prospective, multicenter inception cohort of 226 patients with respiratory failure requiring mechanical ventilation after HSCT. The main outcome measures were determination of a baseline probability of death, drawn from literature review; likelihood ratio of mortality for each prognostic feature determined from the validation cohort; conditional probability of death in the presence of each feature; and 6-month survival of those who recover. Patients requiring mechanical ventilation after HSCT have a baseline probability of death of 82% to 96%. In the setting of combined hepatic and renal dysfunction, the probability of death rises to 98% to 100%. Other previously reported prognostic features are less strongly associated with mortality. For patients who recover from respiratory failure, the proportion surviving 6 months or longer ranges from 27% to 88%. It was concluded that in patients requiring mechanical ventilation after HSCT, the presence of combined hepatic and renal dysfunction is highly predictive of death. The presence of this feature may justify the recommendation to withdraw life-sustaining measures.

Adult↗
PubMed2001

BRCA1 and GADD45 mediated G2/M cell cycle arrest in response to antimicrotubule agents.

BRCA1 is a tumour suppressor gene implicated in the predisposition to early onset breast and ovarian cancer. We have generated cell lines with inducible expression of BRCA1 to evaluate its role in mediating the cellular response to various chemotherapeutic drugs commonly used in the treatment of breast and ovarian cancer. Induction of BRCA1 in the presence of Taxol and Vincristine resulted in a dramatic increase in cell death; an effect that was preceded by an acute arrest at the G2/M phase of the cell cycle and which correlated with BRCA1 mediated induction of GADD45. A proportion of the arrested cells were blocked in mitosis suggesting activation of both a G2 and a mitotic spindle checkpoint. In contrast, no specific interaction was observed between BRCA1 induction and treatment of cells with a range of DNA damaging agents including Cisplatin and Adriamycin. Inducible expression of GADD45 in the presence of Taxol induced both G2 and mitotic arrest in these cells consistent with a role for GADD45 in contributing to these effects. Our results support a role for both BRCA1 and GADD45 in selectively regulating a G2/M checkpoint in response to antimicrotubule agents and raise the possibility that their expression levels in cells may contribute to the toxicity observed with these compounds.

Antineoplastic Agents↗
PubMed2001

A novel carbohydrate-binding protein is a component of the plant cell wall-degrading complex of Piromyces equi.

The recycling of photosynthetically fixed carbon by the action of microbial plant cell wall hydrolases is a fundamental biological process that is integral to one of the major geochemical cycles and, in addition, has considerable industrial potential. Enzyme systems that attack the plant cell wall contain noncatalytic carbohydrate-binding modules (CBMs) that mediate attachment to this composite structure and play a pivotal role in maximizing the hydrolytic process. Anaerobic fungi that colonize herbivores are the most efficient plant cell wall degraders known, and this activity is vested in a high molecular weight complex that binds tightly to the plant cell wall. To investigate whether plant cell wall attachment is mediated by noncatalytic proteins, a cDNA library of the anaerobic fungus Piromyces equi was screened for sequences that encode noncatalytic proteins that are components of the cellulase-hemicellulase complex. A 1.6-kilobase cDNA was isolated encoding a protein of 479 amino acids with a M(r) of 52548 designated NCP1. The mature protein had a modular architecture comprising three copies of the noncatalytic dockerin module that targets anaerobic fungal proteins to the cellulase-hemicellulase complex. The two C-terminal modules of NCP1, CBM29-1 and CBM29-2, respectively, exhibit 33% sequence identity with each other but have no homologues in protein data bases. A truncated form of NCP1 comprising CBM29-1 and CBM29-2 (CBM29-1-2) and each of the two individual copies of CBM29 bind primarily to mannan, cellulose, and glucomannan, displaying the highest affinity for the latter polysaccharide. CBM29-1-2 exhibits 4-45-fold higher affinity than either CBM29-1 or CBM29-2 for the various ligands, indicating that the two modules, when covalently linked, act in synergy to bind to an array of different polysaccharides. This paper provides the first report of a CBM-containing protein from an anaerobic fungal cellulase-hemicellulase complex. The two CBMs constitute a novel CBM family designated CBM29 whose members exhibit unusually wide ligand specificity. We propose, therefore, that NCP1 plays a role in sequestering the fungal enzyme complex onto the plant cell wall.

Amino Acid Sequence↗
PubMed2001

Short-term penicillin-V prophylaxis did not prevent acute otitis media in infants.

OBJECTIVE: To determine whether prophylactic, short-term penicillin V treatment during upper respiratory tract infections can prevent the occurrence of recurrent acute otitis media in young children. METHODS: Seventy children were studied in a prospective, double-blind, placebo-controlled study. All children had suffered their first episode of acute otitis media before the age of 6 months. After inclusion in the study group, administration of penicillin V or placebo was initiated by the parents at subsequent upper respiratory tract infections. The children were examined by otomicroscopy within 3 days after treatment was initiated. The children were scheduled for a total follow-up period of 12 months, including bimonthly visits for check-up irrespective of treatment periods. RESULTS: There were 304 treated episodes of upper respiratory tract infection. There was no significant difference in the number of acute otitis episodes between groups. CONCLUSION: Initiation of penicillin V prophylaxis at upper respiratory tract infection in small children did not prevent recurrent acute otitis media in this study.

Acute Disease↗
PubMed2001

Evidence for synergy between family 2b carbohydrate binding modules in Cellulomonas fimi xylanase 11A.

Glycoside hydrolases often contain multiple copies of noncatalytic carbohydrate binding modules (CBMs) from the same or different families. Currently, the functional importance of this complex molecular architecture is unclear. To investigate the role of multiple CBMs in plant cell wall hydrolases, we have determined the polysaccharide binding properties of wild type and various derivatives of Cellulomonas fimi xylanase 11A (Cf Xyn11A). This protein, which binds to both cellulose and xylan, contains two family 2b CBMs that exhibit 70% sequence identity, one internal (CBM2b-1), which has previously been shown to bind specifically to xylan and the other at the C-terminus (CBM2b-2). Biochemical characterization of CBM2b-2 showed that the module bound to insoluble and soluble oat spelt xylan and xylohexaose with K(a) values of 5.6 x 10(4), 1.2 x 10(4), and 4.8 x 10(3) M(-1), respectively, but exhibited extremely weak affinity for cellohexaose (<10(2) M(-1)), and its interaction with insoluble cellulose was too weak to quantify. The CBM did not interact with soluble forms of other plant cell wall polysaccharides. The three-dimensional structure of CBM2b-2 was determined by NMR spectroscopy. The module has a twisted "beta-sandwich" architecture, and the two surface exposed tryptophans, Trp 570 and Trp 602, which are in a perpendicular orientation with each other, were shown to be essential for ligand binding. In addition, changing Arg 573 to glycine altered the polysaccharide binding specificity of the module from xylan to cellulose. These data demonstrate that the biochemical properties and tertiary structure of CBM2b-2 and CBM2b-1 are extremely similar. When CBM2b-1 and CBM2b-2 were incorporated into a single polypeptide chain, either in the full-length enzyme or an artificial construct comprising both CBM2bs covalently joined via a flexible linker, there was an approximate 18-20-fold increase in the affinity of the protein for soluble and insoluble xylan, as compared to the individual modules, and a measurable interaction with insoluble acid-swollen cellulose, although the K(a) (approximately 6.0 x 10(4) M(-1)) was still much lower than for insoluble xylan (K(a) = approximately 1.0 x 10(6) M(-1)). These data demonstrate that the two family 2b CBMs of Cf Xyn11A act in synergy to bind acid swollen cellulose and xylan. We propose that the increased affinity of glycoside hydrolases for polysaccharides, through the synergistic interactions of CBMs, provides an explanation for the duplication of CBMs from the same family in some prokaryotic cellulases and xylanases.

Actinomycetales↗
PubMed2001

Loss of chromosome arms 3p and 9p and inactivation of P16 (INK4a) in normal epithelium of patients with primary lung cancer.

The accumulation of genetic alterations in the respiratory epithelium may give rise to cancer and often is accompanied by a series of histologic alterations over a period of several years. Recent studies have identified some molecular alterations in histologically normal-appearing epithelium among patients with lung cancer. To extend these observations, we investigated clonal genetic alterations by using fluorescence in situ hybridization (FISH) analysis and immunohistochemistry in 69 biopsy samples of histologically normal-appearing bronchial epithelium from 22 patients with or without lung cancer. Thirty-seven biopsy specimens from 13 patients were examined for loss of 3p14, and 48 biopsy specimens from 18 patients were examined for loss at 9p21 by FISH. P16(INK4a) expression was analyzed in 54 biopsy samples from 19 patients. In at least one biopsy specimen from five of the 13 patients with primary lung cancer, FISH or immunohistochemistry detected loss of the 3p14 or 9p21 region. In contrast, no alterations were detected for the same regions in the nine patients without primary lung cancer. Our results support the concept that the normal epithelial surface of large bronchi of patients with lung cancer has molecular changes suggestive of the outgrowth of numerous clonal foci.

Bronchi↗
PubMed2001

Evaluation of pulmonary infiltrates in critically ill patients with cancer and marrow transplant.

Pulmonary infiltrates in critically ill patients with cancer or marrow transplant can be evaluated by the differential diagnosis presented at the beginning of this article. The patient's quantitative immune system dysfunction, epidemiologic history and chest radiographic findings (pattern, rapidity, and time of onset) will help focus the differential diagnosis. In this patient population, however, common diagnoses can have atypical presentations, unusual diagnoses do occur, and more than one process may be responsible for a patient's infiltrates. Early bronchoscopy to rule out infection is the focus of diagnostic testing. Surgical lung biopsy in this patient population has a low yield.

Algorithms↗
PubMed2001

Characterization of a cellulosome dockerin domain from the anaerobic fungus Piromyces equi.

The recycling of photosynthetically fixed carbon in plant cell walls is a key microbial process. In anaerobes, the degradation is carried out by a high molecular weight multifunctional complex termed the cellulosome. This consists of a number of independent enzyme components, each of which contains a conserved dockerin domain, which functions to bind the enzyme to a cohesin domain within the protein scaffoldin protein. Here we describe the first three-dimensional structure of a fungal dockerin, the N-terminal dockerin of Cel45A from the anaerobic fungus Piromyces equi. The structure contains a novel fold of 42 residues. The ligand binding site consists of residues Trp 35, Tyr 8 and Asp 23, which are conserved in all fungal dockerins. The binding site is on the opposite side of the N- and C-termini of the molecule, implying that tandem dockerin domains, seen in the majority of anaerobic fungal plant cell wall degrading enzymes, could present multiple simultaneous binding sites and, therefore, permit tailoring of binding to catalytic demands.

Amino Acid Sequence↗
PubMed2001

End-stage renal disease: factors affecting referral decisions by family physicians in Canada, the United States, and Britain.

The objective of this study is to determine how patient age, sex, creatinine level, and comorbidity affect referral decisions for the treatment of end-stage renal disease (ESRD) and whether these decisions are affected by physician characteristics in three countries: Canada, the United States, and Britain. A vignette-based questionnaire was mailed to a random sample of family physicians in Ontario, Canada (1,818 physicians); all family physicians in the state of New York (1,814 physicians); and a sample of general practitioners from the south of England (2,228 physicians) in 1996. Physicians were presented with clinical scenarios involving a patient with varying degrees of renal insufficiency and a complicating comorbidity, including angina, diabetes, cancer, mental illness, or socioeconomic circumstances. They were asked to indicate the likelihood of referral. Half the physicians received a questionnaire describing a male patient, and half, a female patient. Mean creatinine levels at which physicians would refer were 260 micromol/L for British physicians, 297 micromol/L for Canadian physicians, and 340 micromol/L for American physicians. No difference in referral rates was found based on the sex of the patient or physician. Sixty-five percent of American and Canadian physicians would refer regardless of patient age, but only 49% of British physicians would do so. Family physicians in the United States, Canada, and Britain function as gatekeepers for patients with ESRD. They are less likely to refer based on increasing severity of comorbid conditions. They also discriminate based on age, but not sex.

Adult↗
PubMed2001

Nutrition-hormone receptor-gene interactions: implications for development and disease.

Nutrition profoundly alters the phenotypic expression of a given genotype, particularly during fetal and postnatal development. Many hormones act as nutritional signals and their receptors play a key role in mediating the effects of nutrition on numerous genes involved in differentiation, growth and metabolism. Polypeptide hormones act on membrane-bound receptors to trigger gene transcription via complex intracellular signalling pathways. By contrast, nuclear receptors for lipid-soluble molecules such as glucocorticoids (GC) and thyroid hormones (TH) directly regulate transcription via DNA binding and chromatin remodelling. Nuclear hormone receptors are members of a large superfamily of transcriptional regulators with the ability to activate or repress many genes involved in development and disease. Nutrition influences not only hormone synthesis and metabolism but also hormone receptors, and regulation is mediated either by specific nutrients or by energy status. Recent studies on the role of early environment on development have implicated GC and their receptors in the programming of adult disease. Intrauterine growth restriction and postnatal undernutrition also induce striking differences in TH-receptor isoforms in functionally-distinct muscles, with critical implications for gene transcription of myosin isoforms. glucose transporters, uncoupling proteins and cation pumps. Such findings highlight a mechanism by which nutritional status can influence normal development, and modify nutrient utilization. thermogenesis. peripheral sensitivity to insulin and optimal cardiac function. Diet and stage of development will also influence the transcriptional activity of drugs acting as ligands for nuclear receptors. Potential interactions between nuclear receptors, including those for retinoic acid and vitamin D, should not be overlooked in intervention programmes using I or vitamin A supplementation of young and adult human populations

Diet↗
PubMed2001

Long-term average spectrum (LTAS) analysis of sex- and gender-related differences in children's voices.

Long-term average spectrum (LTAS) analysis offers representative information on voice timbre providing spectral information averaged over time. It is particularly useful when persistent spectral features are under investigation. The aim of this study was to compare perceived sex of children to the LTAS analysis of their audio signals. A total of 320 children, aged between 3 and 12 years, were recorded singing a song. In an earlier analysis, the recorded voices were evaluated with respect to perceived and actual sex by experienced listeners. From this group, a subgroup of 59 children (30 boys and 29 girls) was selected. The mean LTAS revealed a peak at 5 kHz for children perceived with confidence as boys, and a flat spectrum at 5 kHz for children perceived confidently as girls (whether male or female in actuality).

Child↗
PubMed2001

GPs' views of discussions of prognosis in severe COPD.

BACKGROUND: Modern palliative care promotes open communication between doctor and patient, which includes access to information about prognosis. GPs play a major role in managing chronic obstructive pulmonary disease (COPD) patients in the final stages of illness. Their views of discussions of prognosis are therefore important if the principles of palliative care are to be extended to COPD. OBJECTIVE: Our aim was to investigate the role that discussions of prognosis play in GPs' management of patients with severe COPD and the factors that influence those discussions. METHODS: We conducted a questionnaire survey of all GP principals of one inner London Health Authority (n = 389) in April 1999. Questionnaire development involved a literature review to identify issues of importance to GPs in the discussion of prognosis in COPD, and in-depth interviews with five GPs. RESULTS: Of the 214 respondents (55% response), 72.5% thought that discussions of prognosis were often necessary or essential in severe COPD. The majority (82%) felt that GPs have an important role in these discussions. However, only a minority (41%) of GPs reported often or always discussing prognosis. Half the GPs were undecided as to whether most patients with COPD wanted to know about their prognosis. Among the GPs who reported rarely or never discussing prognosis (n = 33), a majority felt ill-prepared to discuss the subject (60% reported that there was insufficient information in the primary care notes to be able to discuss prognosis, and 64% found it hard to start discussions with patients). CONCLUSION: Although the majority of GPs acknowledged a need to discuss prognosis in severe COPD, this was not reflected in their reported behaviour. It appears that the palliative care approach of open communication, whilst seen to be relevant to severe COPD, is not applied routinely in managing the disease in primary care. Uncertainty among GPs as to how patients view the discussion of prognosis and inadequate preparation may pose potential barriers.

Adult↗