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Biomedical subjects

V Murray

Publications and source records attributed to V Murray.

At least 37 records · Page 2Linked to original sources
PubMed2001

Does breastfeeding protect children from asthma? Analysis of NHANES III survey data.

We sought to determine whether breastfeeding (yes/no) or its duration protects against the development of childhood asthma, its severity or age of onset. We conducted a secondary analysis of youth files of the National Health and Nutrition Examination Survey III (1988-94), and reviewed data from 6,783 children age 2 months to 6 years (3,316 breastfed), excluding children with a history of low birth weight or treatment in a neonatal intensive care unit. Study participants were breastfed an average of 157 days. The average age at onset of asthma was 14.3 months. In the logistic regression model, "ever breast-fed" was not a significant protective factor for developing asthma. Significant predictive factors were the mother's age at child's birth (beta = -0.08, p < 0.01), and a parent having asthma or hayfever (beta = 0.46, p < 0.01). In the linear regression model, the duration of breastfeeding was not a predictor for age at onset of asthma (beta = 0.01, p = 0.53). Only maternal smoking during pregnancy was a significant predictor of age at onset of asthma (beta = -7.59, p < 0.01). Breastfeeding does not appear to prevent asthma, delay its onset, or reduce its severity. However, breastfeeding is still recommended for its many other benefits.

Age Distribution↗
PubMed2000

The effect of chromatin structure on cisplatin damage in intact human cells.

The influence of chromatin structure on cisplatin DNA damage was investigated in intact human cells. The epsilon-globin gene promoter was utilised as the target DNA sequence and the terminal transferase-dependent PCR technique was employed to examine adduct formation at base pair resolution. It was found that cisplatin preferentially damaged at runs of consecutive guanine bases in intact cells. By comparing the relative intensity of adduct formation in intact cells and in purified genomic DNA, it was possible to assess the influence of chromatin proteins on the extent of cisplatin DNA damage. Enhanced damage in intact cells was found at the CACC site where a member of the Sp1 family of proteins is thought to bind. It is postulated that protein binding at this site bends the DNA double-helix so that enhanced cisplatin binding occurs. The altered DNA binding of cisplatin in the presence of chromatin proteins could be important in the properties of cisplatin as an anti-tumour drug.

Antineoplastic Agents↗
PubMed2000

Interaction of cisplatin and DNA-targeted 9-aminoacridine platinum complexes with DNA.

Interaction of acridine- and 9-aminoacridinecarboxamide platinum complexes with DNA was investigated with respect to their DNA sequence specificity and kinetics of binding. The DNA sequence specificity of the compounds was quantitatively analyzed using a polymerase stop assay with the plasmid pUC19. The 9-aminoacridinecarboxamide platinum complexes exhibited a different sequence specificity to that of cisplatin, shifted away from runs of consecutive guanines (the main binding site for cisplatin). This alteration was dependent on chain length. Shorter chain length compounds (n = 2, 3) showed a greater difference in sequence specificity, while longer chain length compounds (n = 4, 5) more closely resembled cisplatin. An acridinecarboxamide platinum complex showed a similar sequence specificity to cisplatin, revealing that the major change of sequence specificity was due to the presence of the 9-amino substituent. A linear amplification system was used to investigate the time course of the reaction. The presence of an intercalating group (acridinecarboxamide or 9-aminoacridinecarboxamide) greatly increased the rate of reaction with DNA; this is proposed to be due to a different reaction mechanism with DNA (direct displacement by the N-7 of guanine).

Acridines↗
PubMed2000

A large "footprint" at the boundary of the human beta-globin locus control region hypersensitive site-2.

The 5'-boundary region of the human beta-globin locus control region hypersensitive site-2 (HS-2) was examined for protein-DNA interactions. The HS-2 is an erythroid specific DNase I hypersensitive site that extends for approximately 600 bp. Erythroid K562 cells and non-erythroid HeLa cells were damaged by bleomycin and hedamycin--these agents are able to "footprint" nucleosome cores and proteins bound to DNA. The fragments generated by DNA damage were amplified by the ligation-mediated polymerase chain reaction with primers specific for the 5'-boundary region of HS-2 and examined at base pair resolution on DNA sequencing gels. The intensity of damage in intact cells was compared with that in purified DNA. The comparison between intact cells and purified DNA revealed a protected region of 226 bp with bleomycin and 182 bp with hedamycin in K562 cells. The length of the protected region was consistent with the presence of a nucleosome core. We postulate that an erythroid-specific protein binds next to the positioned nucleosome at the boundary of HS-2 to prevent sliding of the nucleosome into the hypersensitive site--this would also account for the large size of the protected region. HeLa cells (lacking a hypersensitive site in the beta-globin cluster) did not have an area of protection in this region.

Anthraquinones↗
PubMed2000

Possible immediate and long-term health effects following exposure to chemical warfare agents.

Agents of chemical warfare continue to pose a threat to human life. Organophosphorus compounds are possibly the best known and most used agents in recent times. These are known to produce acute ill health and death and, probably equally important, many diverse delayed effects, many of which are not clinically nor pathologically well defined. The immediate and delayed effects of organophosphorus compounds, in particular, and those of other known agents of chemical warfare, such as mustard gas, Lewisite, phosgene, cyanides and the newer crowd control agents, are reviewed. Environmental sequelae of these agents are gaining importance as probable causes of chronic ill health amongst those living in regions where these agents have been used. The need to study the pattern of disease in exposed populations is emphasised.

Animals↗
PubMed2000

The capability of accident and emergency departments to safely decontaminate victims of chemical incidents.

OBJECTIVES: To evaluate the capability of accident and emergency (A&E) departments in six health regions of England to safely decontaminate casualties exposed to hazardous chemicals. METHODS: In January 1999 a postal questionnaire was sent to the clinical director of all A&E departments in Trent, North and South Thames, South and West, North West and, Anglia and Oxford Health Regions. The questionnaire inquired about characteristics of the department, decontamination facilities and equipment, and staff training. Nonresponders were sent a second questionnaire and contacted by telephone if they failed to respond to the second mailing. RESULTS: 308 of 326 departments identified (94%) returned a questionnaire. There was no significant difference in response rate by region (p = 0.99). Analysis was restricted to 154 major departments seeing more than 20000 new attendances per year. Of these 154 departments, 109 (71%) had a written chemical incident plan but only 55 (36%) maintained a list of nearby industrial chemical sites. Fifty nine departments (38%) stated that members of staff had received training in the management of chemically contaminated casualties in the preceding year. Eighteen departments (12%) possessed the level of personal protective equipment (PPE) recommended for decontamination by the Ambulance Services Association. Ninety six departments (62%) had a designated decontamination room but only seven (7%) of them incorporated all the features generally considered necessary for safe decontamination. Forty one units (27%) had the capability to decontaminate casualties outside of the department either with warm water from a shower attachment or with a mobile decontamination unit. Thirty six departments (23%) had neither a decontamination room nor the ability to decontaminate casualties outside the department. Only 16 units (10%) had both adequate PPE and either a decontamination room or the capability to decontaminate outside the department. CONCLUSIONS: This study has identified deficiencies in the current NHS capability to respond to chemical incidents. To resolve this, nationally recognised standards for decontamination facilities, equipment and training should be formulated, agreed and implemented.

Chi-Square Distribution↗
PubMed2000

Survey of how public health doctors in the United Kingdom and Republic of Ireland investigate the effects of long-term exposure to point sources of chemicals.

Public health departments may need to investigate the health effects of long term exposures to chemicals from sources such as landfill sites and factories. Public health consultants responsible for communicable disease and environmental health and directors of public health in all health authorities and health boards in the United Kingdom and the Republic of Ireland were surveyed on behalf of a Faculty of Public Health Medicine guideline development group. The survey achieved a response rate of over 80%. Most public health doctors had investigated the health effects of long term exposure to chemicals, but many found it difficult to conduct effective and appropriate investigations in the face of community and political pressure. Most doctors acknowledged that they were responsible for investigating these problems, but wanted more epidemiological support, training, and guidance.

Attitude of Health Personnel↗
PubMed2000

Use of paracetamol (acetaminophen) for suicide and nonfatal poisoning: worldwide patterns of use and misuse.

Paracetamol (acetaminophen) is one of the most frequently used drugs in intentional overdoses. We have investigated associations between its availability and its use for overdose and suicide around the world by means of a postal questionnaire and literature review. Countries that limit the quantity of paracetamol available in a single purchase generally report lower rates of paracetamol-related morbidity and mortality. National policy decisions regarding restrictions on its availability need to weigh the inconvenience caused to the many who use the drug safely against those of the few in whom overdose may be fatal. We recommend restricting the quantity of drug available as a single purchase as the most pragmatic means of reducing paracetamol-related suicide and liver failure.

Acetaminophen↗
PubMed1999

Protein-DNA footprinting of the human epsilon-globin promoter in human intact cells using nitrogen mustard analogues and other DNA-damaging agents.

Nitrogen mustard analogues, bleomycin and dimethyl sulphate (DMS) have been used as probes of protein-DNA interactions in intact human cells. The sites of damage have been determined at base pair resolution in the single copy epsilon-globin gene promoter in erythroid K562 cells, non-erythroid HeLa cells and purified DNA. Exponential amplification of gene-specific damage fragments was achieved using the ligation-mediated polymerase chain reaction (LMPCR) technique and analysed on DNA sequencing gels. A comparison of the relative damage band intensities between purified DNA and intact cells revealed several significant differences - both protection (footprint) and enhancement. These differences occurred at putative transcription factor binding sites and hence are thought to be due to protein-DNA interactions. A major feature of the band intensity ratio plots was the footprint observed at the CCAAT box binding motif as revealed by nitrogen mustard analogues. Enhanced band intensity (hypersensitivity) was displayed at the 5'- and 3'-ends of the CCAAT box in K562 cells - this feature was absent in HeLa cells and in vitro reconstitutions. A footprint was found at the GATA-1 motif in K562 cells that was also absent in non-expressing HeLa cells. Footprints were also evident at the TATA box, CACC box and the epsilonF1 DNA binding motif in K562 cells.

Bleomycin↗
PubMed1999

A survey of the sequence-specific interaction of damaging agents with DNA: emphasis on antitumor agents.

This article reviews the literature concerning the sequence specificity of DNA-damaging agents. DNA-damaging agents are widely used in cancer chemotherapy. It is important to understand fully the determinants of DNA sequence specificity so that more effective DNA-damaging agents can be developed as antitumor drugs. There are five main methods of DNA sequence specificity analysis: cleavage of end-labeled fragments, linear amplification with Taq DNA polymerase, ligation-mediated polymerase chain reaction (PCR), single-strand ligation PCR, and footprinting. The DNA sequence specificity in purified DNA and in intact mammalian cells is reviewed for several classes of DNA-damaging agent. These include agents that form covalent adducts with DNA, free radical generators, topoisomerase inhibitors, intercalators and minor groove binders, enzymes, and electromagnetic radiation. The main sites of adduct formation are at the N-7 of guanine in the major groove of DNA and the N-3 of adenine in the minor groove, whereas free radical generators abstract hydrogen from the deoxyribose sugar and topoisomerase inhibitors cause enzyme-DNA cross-links to form. Several issues involved in the determination of the DNA sequence specificity are discussed. The future directions of the field, with respect to cancer chemotherapy, are also examined.

Antineoplastic Agents↗
PubMed1999

Plasma semicarbazide-sensitive amine oxidase in stroke.

Semicarbazide-sensitive amine oxidase (SSAO) has been suggested to be involved in the development of vascular endothelial damage. The source of the soluble form of SSAO found in the blood serum is unknown. However, it has been speculated that it is secreted from cells within the vascular wall where high activity of the enzyme is found. Altered SSAO activity has been reported in atherosclerotic plaques of the human aorta. Stroke is a manifestation of long-term atherosclerotic disease, and in this study, plasma SSAO activities were estimated in 42 patients with cerebral thrombosis and 26 patients with cerebral embolism, and compared to two control groups of 45 individuals in total. No statistically significant differences were found between the patient groups and controls regarding plasma SSAO activity, suggesting that changes in the soluble form of SSAO found in the circulation do not play a major role in this type of acute cerebrovascular event. Furthermore, it does not seem likely that the involvement of vascular tissue occurring in stroke results in release of the enzyme into the circulation. Nevertheless, further studies on tissue-bound SSAO in cerebral vessels would be of great interest.

Aged↗
PubMed1999

Outbreak of gastroenteritis associated with contamination of a private borehole water supply.

An outbreak of gastroenteritis affected 58 of 700 people served by a private water supply at a biological research institute located in a village. No cases were detected in 250 residents of the same village served by a public water supply over the same period. Consumer complaints of tainting and laboratory evidence of bacterial and chemical contamination were obtained for the private water supply, but not for the public water supply. The outbreak was probably caused by contamination from a nearby sewer of a borehole used for the private supply. The outbreak showed how a large, private water supply posed a substantial risk to public health. The regulatory framework for such water supplies should be modified to ensure their safer design and operation.

Adolescent↗
PubMed1999

Asthma care in community health centers: a study by the southeast regional clinicians' network.

Federally funded community health centers (CHCs) were surveyed to assess their ability to serve low-income asthma patients in the southeastern United States. Data were collected on CHC clinicians, pharmacy services, and patient characteristics. Twenty-six (74%) of 35 participating CHCs provided data on 83 distinct clinic sites in eight states, representing 898,977 billable patient visits to 318,920 people during the one-year study period. Participating CHCs provided 23% of all CHC patient visits in Region IV in 1995. Sixty-two percent of patients had a family income below poverty level. Almost 75% of the patients were uninsured or receiving Medicaid. Asthma was the diagnosis code for 2.04% of all medical encounters. Twenty-nine percent of sites were unable to provide medications for uninsured asthma patients, while 66% could provide drug samples. Thirty-three percent of CHCs had in-house pharmacies and 33% offered pharmacy vouchers. Eighty-two percent could provide beta-agonist inhalers, 54% could provide steroid inhalers, and 17% could provide peak flow meters. Federally funded CHCs provide care to many asthma patients from the highest risk segments of the population, but often do not have the resources needed to follow current clinical guidelines.

Adrenergic beta-Agonists↗