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Biomedical subjects

R Hayward

Publications and source records attributed to R Hayward.

At least 19 recordsLinked to original sources
PubMed2001

A naturalistic study on ending blind dosing in a methadone maintenance clinic in Israel.

Since many methadone maintenance treatment (MMT) clinics in the United States do not share with patients, information concerning their methadone dosage, we aimed to investigate the impact of patients being informed of their methadone dosage and the influence of ending blind dosing on treatment outcome. Seventy-four patients who were unaware of their methadone dosage took part in this study. We compared changes in opiate abuse, levels of methadone dosage and patients' perceptions of dosage adequacy before and after they were informed of their dosage. Data on opiate abuse were based upon bi-weekly randomly taken and observed urine tests provided the data on opiate abuse. Records on methadone dosage were kept and a short questionnaire on dosage-related attitudes, devised for this study, was administered. Most patients expressed the desire to know their dosage, but there were no significant changes in opiate abuse, methadone dosage or the patients' perceptions of dosage adequacy after they knew what it was. We conclude that informing patients of their methadone dosage and thereby ending blind dosing does not seem to have any negative effect on treatment outcomes. We believe that this policy is in accord with the patients' rights and expressed will to know their dosage and this justifies putting an end to blind dosing policies.

Chi-Square Distribution↗
PubMed2001

Identification of extensive genomic loss and gain by comparative genomic hybridisation in malignant astrocytoma in children and young adults.

Although astrocytomas are the most common central nervous system tumours in all age groups, there is substantial evidence that tumours arising in young patients (< 25 years of age) do not have the same genetic abnormalities that are characteristic of tumours in older patients. Furthermore, novel, consistent changes have not been identified in astrocytomas in children and young adults. We analysed 13 malignant astrocytomas from young patients using comparative genomic hybridisation. Regions of genomic imbalance were identified in 10 cases. The most common recurrent copy number aberrations were loss of 16p (54% of cases), 17p (38%), 19p (38%), and 22 (38%) and gain on 2q (38%), 12q (38%), 13 (38%), 4q (31%), 5q (31%), and 8q (31%). Seven regions of high copy number amplification were observed at 8q21-22 (three cases), 7q22-23 (two cases), and 1p21-22, 2q22, 12q13-pter, 12q15-21, and 13q11-14 (one case each). This study provides evidence of new characteristic chromosomal imbalances from which potential candidate genes involved in the development of malignant astrocytoma in children and young adults may be identified.

Adolescent↗
PubMed2001

Gain of 1q and loss of 22 are the most common changes detected by comparative genomic hybridisation in paediatric ependymoma.

Ependymomas are the third most common brain tumour in the paediatric population. Although cytogenetic and molecular analyses have pinpointed deletions of chromosomes 6q, 17, and 22 in a subset of tumours, definitive patterns of genetic aberrations have not been determined. In the present study, we analysed 40 ependymomas from paediatric patients for genomic loss or gain using comparative genomic hybridisation (CGH). Eighteen of the tumours (45%) had no detectable regions of imbalance. In the remaining cases, the most common copy number aberrations were loss of 22 (25% of tumours) and gain of 1q (20%). Three regions of high copy number amplification were noted at 1q24-31 (three cases), 8q21-23 (two cases), and 9p (one case). Although there was no association with the loss or gain of any chromosome arm or with benign versus anaplastic histologic characteristics, the incidence of gain of 7q and 9p and loss of 17 and 22 was significantly higher in recurrent versus primary tumours. This study has identified a number of chromosomal regions that may contain candidate genes involved in the development of different subgroups of ependymoma.

Adolescent↗
PubMed2001

The tortoise and the love-machine: Grey Walter and the politics of electroencephalography.

The life of the pioneer electroencephalographer, William Grey Walter, initially appears to be a paradigmatic example of the process of network building and delegation identified by Michel Callon and Bruno Latour. In his professional career, Walter continually repositioned himself, moving from an unhappy beginning as an expert in the apparently unless and suspect technology of the EEG, to become a self-styled crucial mediator in subjects as diverse as medical diagnosis, forensic detection, marriage counseling, and international diplomacy. This position was achieved moreover through the construction and co-option of human and mechanical accomplices - laboratory assistants, electrical tortoises, and mechanical analyzers - which sustained his research and propagated his arguments. However in contrast to Callon and Latour's atomistic account of scientific power and agency, this paper will extend their analysis to explore the impact of network building and delegation on domestic life, human desire, and personal identity. Walter's engagement with the complexities of love and the human brain demonstrates how the transformative power of scientific rhetoric extends simultaneously into both the organization of the world and the subjectivity of the individual.

Electroencephalography↗
PubMed2001

Fostering an Internet-based work group in community health through action research.

In this article, we describe an action research study to foster an Internet-based work group as part of a two-year community health research training program in Alberta, Canada. The objectives of our study were to incorporate Internet-based technology into the program, establish a distributed work group over time, and reflect on the lessons learned. The participants represented seventeen health regions. There were thirty-five instructors and expert resource persons (varied over time), two training coordinators, four support staff, a program coordinator, two action researchers, and two independent consultants. The data collected included program documents, phone interviews, online surveys, meeting notes, online discussions, computer usage log, site visits, keystroke entry logs, help desk logs, and program evaluation reports. Content analysis was conducted with NUD*IST to identify concepts and themes from the data. Our findings suggest that role clarification, facilitative support, network linkages, and workplace learning are important aspects of fostering Internet-based work groups in a health setting, where members strive to establish themselves, seek meaning in their work, support each other, and add value to their organizations.

Canada↗
PubMed2000

Mutation analysis and embryonic expression of the HLXB9 Currarino syndrome gene.

The HLXB9 homeobox gene was recently identified as a locus for autosomal dominant Currarino syndrome, also known as hereditary sacral agenesis (HSA). This gene specifies a 403-amino acid protein containing a homeodomain preceded by a very highly conserved 82-amino acid domain of unknown function; the remainder of the protein is not well conserved. Here we report an extensive mutation survey that has identified mutations in the HLXB9 gene in 20 of 21 patients tested with familial Currarino syndrome. Mutations were also detected in two of seven sporadic Currarino syndrome patients; the remainder could be explained by undetected mosaicism for an HLXB9 mutation or by genetic heterogeneity in the sporadic patients. Of the mutations identified in the 22 index patients, 19 were intragenic and included 11 mutations that could lead to the introduction of a premature termination codon. The other eight mutations were missense mutations that were significantly clustered in the homeodomain, resulting, in each patient, in nonconservative substitution of a highly conserved amino acid. All of the intragenic mutations were associated with comparable phenotypes. The only genotype-phenotype correlation appeared to be the occurrence of developmental delay in the case of three patients with microdeletions. HLXB9 expression was analyzed during early human development in a period spanning Carnegie stages 12-21. Signal was detected in the basal plate of the spinal cord and hindbrain and in the pharynx, esophagus, stomach, and pancreas. Significant spatial and temporal expression differences were evident when compared with expression of the mouse Hlxb9 gene, which may partly explain the significant human-mouse differences in mutant phenotype.

Abnormalities, Multiple↗
PubMed2000

Chemosensitivity in childhood brain tumours in vitro: evidence of differential sensitivity to lomustine (CCNU) and vincristine.

The aim of this study was to examine the range of sensitivity of a panel of short-term cultures derived from different types of malignant childhood brain tumours including medulloblastoma, ependymoma and glioblastoma multiforme to three cytotoxic drugs, lomustine (CCNU), vincristine (VCR) and procarbazine (PCB). Sensitivity was assessed using a modification of the dimethylthiazolyl-2,5-diphenyl tetrazolium bromide (MTT) assay. Short-term cell lines derived from ependymomas were considerably more resistant to VCR than other types of childhood brain tumours, while cultures derived from supratentorial primitive neuroectodermal tumour (PNET) displayed marked sensitivity to both lomustine and VCR. Cultures from ependymomas, medulloblastoma and astrocytic gliomas had similar sensitivity to lomustine and PCB as cultures derived from adult malignant astrocytoma.

Adult↗
PubMed2000

A pilot study of primary care workers with a disability.

Eighty practice managers identified 55 colleagues with disabilities in a postal survey. Most of the 15 people with disabilities who were subsequently interviewed described colleagues having helpful attitudes but changes had not been made to practice workplaces or systems to retain them at work. Proactive support for disabled workers might improve retention in the National Health Service workforce.

Adult↗
PubMed1999

The chitinase PfCHT1 from the human malaria parasite Plasmodium falciparum lacks proenzyme and chitin-binding domains and displays unique substrate preferences.

Within hours after the ingestion of a blood meal, the mosquito midgut epithelium synthesizes a chitinous sac, the peritrophic matrix. Plasmodium ookinetes traverse the peritrophic matrix while escaping the mosquito midgut. Chitinases (EC 3.2.1.14) are critical for parasite invasion of the midgut: the presence of the chitinase inhibitor, allosamidin, in an infectious blood meal prevents oocyst development. A chitinase gene, PgCHT1, recently has been identified in the avian malaria parasite P. gallinaceum. We used the sequence of PgCHT1 to identify a P. falciparum chitinase gene, PfCHT1, in the P. falciparum genome database. PfCHT1 differs from PgCHT1 in that the P. falciparum gene lacks proenzyme and chitin-binding domains. PfCHT1 was expressed as an active recombinant enzyme in Escherichia coli. PfCHT1 shares with PgCHT1 a substrate preference unique to Plasmodium chitinases: the enzymes cleave tri- and tetramers of GlcNAc from penta- and hexameric oligomers and are unable to cleave smaller native chitin oligosaccharides. The pH activity profile of PfCHT1 and its IC(50) (40 nM) to allosamidin are distinct from endochitinase activities secreted by P. gallinaceum ookinetes. Homology modeling predicts that PgCHT1 has a novel pocket in the catalytic active site that PfCHT1 lacks, which may explain the differential sensitivity of PfCHT1 and PgCHT1 to allosamidin. PfCHT1 may be the ortholog of a second, as yet unidentified, chitinase gene of P. gallinaceum. These results may allow us to develop novel strategies of blocking human malaria transmission based on interfering with P. falciparum chitinase.

Acetylglucosamine↗
PubMed1999

Simvastatin preserves the ischemic-reperfused myocardium in normocholesterolemic rat hearts.

BACKGROUND: Ischemia followed by reperfusion in the presence of polymorphonuclear leukocytes (PMNs) results in cardiac contractile dysfunction as well as cardiomyocyte injury. These deleterious effects are due in large part to endothelial dysfunction leading to the upregulation of cell adhesion molecules and subsequent neutrophil-endothelium interaction. At clinically relevant doses, simvastatin, an HMG-CoA reductase inhibitor, has been shown to lower serum cholesterol levels and normalize endothelial cell function. We wanted to test the effects of simvastatin on neutrophil-mediated cardiac dysfunction in a controlled model of myocardial ischemia-reperfusion. METHODS AND RESULTS: This study examines the effects of simvastatin in a neutrophil-dependent isolated perfused rat heart model of ischemia (I) (20 minutes) and reperfusion (R) (45 minutes) injury. Administration of simvastatin 25 micrograms/rat improved coronary flow and preserved left ventricular developed pressure (LVDP) and dP/dtmax, indexes of cardiac contractile function. Final LVDP was 95+/-5 mm Hg in I/R hearts perfused with PMNs and simvastatin, compared with 49+/-4 mm Hg in PMN-perfused I/R hearts receiving only vehicle (P<0.001). In addition, simvastatin significantly reduced PMN accumulation in the ischemic myocardium (P<0.01). In PMN-perfused rat hearts after I/R, simvastatin also significantly attenuated P-selectin expression, CD18 upregulation in rat PMNs, and PMN adherence to rat vascular endothelium. Significant, although less potent, effects were obtained with pravastatin. CONCLUSIONS: These results provide evidence that HMG-CoA reductase inhibitors are potent and effective cardioprotective agents that inhibit leukocyte-endothelial cell interactions and preserve cardiac contractile function and coronary perfusion after myocardial ischemia and reperfusion. Moreover, these effects are unrelated to the cholesterol-lowering action of this agent and appear to be mediated by enhanced endothelial release of NO.

Animals↗
PubMed1999

Characteristics of benzodiazepine abuse in methadone maintenance treatment patients: a 1 year prospective study in an Israeli clinic.

We aimed to study the prevalence patterns and course of benzodiazepine (BZD) abuse in an Israeli methadone maintenance (MMT) clinic using repeated random observed urine analysis as well as self-report data. Lifetime and current prevalence of BZD abuse were found in 66.3 and 50.8% patients, respectively. It was found that 44.6% of patients who abused BZDs during their first month of treatment ceased to do so after 1 year, while 27.4% who had not abused BZDs at the beginning of MMT did so after 1 year in treatment. Flunitrazepam was the most commonly abused BZD (92.9%), followed by diazepam (54.3%) and oxazepam (38.6%). Most of the patients swallowed BZDs (92.8%), 42.9% also smoked or snorted them while 8.6% injected BZDs intravenously. BZDs were used as self-medication for alleviating emotional problems rather than for recreational or other reasons. We conclude that BZD abuse is a significant clinical problem in heroin addicts both before entering and during MMT. MMT may have a positive as well as a negative influence on BZD abuse with the former being more prevalent.

Adult↗
PubMed1999

The present and future management of childhood craniopharyngioma.

Childhood craniopharyngiomas are rare tumours that present formidable difficulties in their treatment if cure is to be achieved without producing severe hypothalamic damage. Experience with our own cases suggests that the morbidity from an attempted radical removal can be predicted - allowing a treatment algorithm to be devised that combines both surgery (radical and "conservative") and radiotherapy (both external fractionated and intra-cyst instillations) in order to achieve long-term tumour control that is not at the expense of a severe functional disability.

Algorithms↗
PubMed1999

Sacral dysgenesis associated with terminal deletion of chromosome 7q: a report of two families.

UNLABELLED: Most cases of sacral dysgenesis are considered to be sporadic events. We present two families in whom the presence of associated clinical features prompted specific investigation of chromosome 7, leading to the identification of an underlying chromosome 7q deletion causing sacral dysgenesis. All affected individuals had microcephaly and developmental delay. Detailed cytogenetic studies confirmed that all three affected individuals had a deletion of chromosome 7q associated with their sacral dysgenesis, developmental delay and related problems. The three affected patients were studied clinically, radiologically and cytogenetically. Eleven unaffected individuals from the two families were also investigated by genetic studies, specifically evaluating chromosome 7. CONCLUSION: It is important that detailed family history, evaluation of associated malformations and the overall clinical picture be considered in identifying the underlying diagnosis in cases of anal stenosis/sacral agenesis. The cases we present demonstrate the value of detailed chromosome studies in such situations.

Abnormalities, Multiple↗
PubMed1999

Recombinant soluble P-selectin glycoprotein ligand-1 protects against myocardial ischemic reperfusion injury in cats.

OBJECTIVE: Neutrophils (PMNs) contribute importantly to the tissue injury associated with ischemia and subsequent reperfusion of a vascular bed. The effects of a recombinant soluble human form of P-selectin glycoprotein ligand-1 (rsPSGL.Ig) on PMN-endothelial cell interactions were investigated in a well established model of feline myocardial-ischemia reperfusion injury. METHODS: Cats were subjected to 90 min of myocardial ischemia followed by 270 min of reperfusion. RESULTS: Administration of rsPSGL.Ig (1 mg/kg) just prior to reperfusion resulted in a significant reduction in myocardial necrosis compared to that in cats administered a low affinity mutant form of rsPSGL.Ig (1 mg/kg) (16 +/- 3 vs. 42 +/- 7% of area-at-risk, P < 0.01). Cardioprotective effects were confirmed by significant (P < 0.05) reductions in plasma creatine kinase activity in cats treated with rsPSGL.Ig. Inhibition of PMN-endothelial cell interactions was evidenced by a significant attenuation in cardiac myeloperoxidase activity (P < 0.01) and reduced PMN adherence to ischemic-reperfused coronary endothelium (P < 0.001). In addition, rsPSGL.Ig treatment significantly (P < 0.01) preserved endothelium-dependent vasorelaxation in ischemic-reperfused coronary arteries. CONCLUSION: These results demonstrate that the administration of a recombinant soluble PSGL-1 reduces myocardial reperfusion injury and preserves vascular endothelial function, which is largely the result of reduced PMN-endothelial cell interactions.

Analysis of Variance↗
PubMed1999

Further evidence from two families that craniofrontonasal dysplasia maps to Xp22.

Craniofrontonasal dysplasia (CFND) is a rare X-linked disorder that maps to a 13-cM region on Xp22. Phenotypic features include craniosynostosis, hypertelorism and a broad nasal root with or without a bifid nasal tip. Multiple examples have been reported of males having a less severe phenotype than females. We report haplotype analyses in two CFND families over the critical region to which the gene has been mapped. In pedigree 1, a clinically unaffected male inherited the affected marker haplotype spanning the critical region. We suggest that this individual does have the CFND mutation, but has an extremely mild phenotype that is not detectable with clinical examination. Under the assumption that he is an unknown phenotype, a combined two-point LOD score of 1.68 at zero recombination was obtained, increasing the previously reported total to 5.61 (DXS8022). The data do not narrow down the critical region. This result stresses the importance of subjecting fathers of apparently sporadic cases to a highly critical medical examination and may also explain the unequal ratio of reported female-to-male cases.

Craniofacial Abnormalities↗