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Biomedical subjects

D Wild

Publications and source records attributed to D Wild.

At least 19 recordsLinked to original sources
PubMed2002

The level of haemoglobin in anaemic cancer patients correlates positively with quality of life.

The aim of this study was to assess the relationship between haemoglobin level and quality-of-life in anaemic cancer patients. Patients, diagnosed with one of four cancers, were recruited if their haemoglobin level was <12 g dl(-1) (female) or <13 g dl(-1) (male). The condition-specific Functional Assessment of Cancer Therapy-Anaemia and the generic SF-36 were used to assess quality-of-life. Thirty-six per cent of the 179 recruited patients had breast cancer, 28% ovarian cancer, 25% lung cancer, and 11% multiple myeloma. Their mean (s.d.) haemoglobin level was 10.66 (1.04) g dl(-1). Partial correlations controlling for the potentially confounding effects of age, gender, and time since diagnosis found significant positive relationships between haemoglobin and all domains of the Functional Assessment of Cancer Therapy-Anaemia, and with all but two of the SF-36 domains. On linear regression controlling for the same factors, each unit haemoglobin rise equalled an average 8.19 Functional Assessment of Cancer Therapy-Anaemia, and an average 6.88 Functional Assessment of Cancer Therapy-Fatigue, increase. Haemoglobin accounted for a similar amount of variability (8%) in SF-36 scores. In conclusion, quality-of-life has been found to be significantly positively related to haemoglobin level in anaemic cancer patients. This suggests that normalisation of haemoglobin in cancer patients is likely to increase their quality-of-life. The greater sensitivity of the condition-specific Functional Assessment of Cancer Therapy-Anaemia compared with the generic SF-36 suggests that the Functional Assessment of Cancer Therapy-Anaemia can be used alone to assess quality-of life in this patient group.

Adult↗
PubMed2001

Sildenafil (Viagra)-induced spontaneous intracerebral haemorrhage.

Sildenafil (Viagra) has been developed as a drug to help male impotence. It has a direct effect on the vasculature of the corpus cavernosum. A case of spontaneous intracerebral haemorrhage (ICH) following the illicit use of Viagra is reported. A discussion of drug-induced ICH is included.

Adult↗
PubMed2000

Recommendations for the categorization of germ cell mutagens.

Germ cell mutagens are currently classified into three categories in the German List of MAK and BAT Values. These categories have been revised and extended by analogy with the new categories for carcinogenic chemicals. Germ cell mutagens produce heritable gene mutations, and heritable structural and numerical chromosome aberrations in germ cells. The original categories 1 and 2 for germ cell mutagens remain unchanged. Two new categories 3A and 3B are proposed for chemicals suspected to be germ cell mutagens. A new category 5 is proposed for germ cell mutagens with low potency that contribute negligibly to human genetic risk provided the MAK value is observed.

Germ Cells↗
PubMed2000

Self-report quality of life measure for people with schizophrenia: the SQLS.

BACKGROUND: Quality of life is the subject of growing interest and investigation. AIMS: To develop and validate a short, self-report quality of life questionnaire (the Schizophrenia Quality of Life Scale, SQLS). METHOD: People with schizophrenia in Liverpool were recruited via the NHS. Items, generated from in-depth interviews, were developed into an 80-item self-report questionnaire. Data were factor analysed, and a shorter form measure was tested for reliability and validity. This measure was administered together with other self-report measures--SF-36, GHQ-12 and HADS--to assess validity. RESULTS: Data were analysed to produce a final 30-item questionnaire, comprising three scales ('psychosocial', 'motivation and energy', and 'symptoms and side-effects') addressing different SQLS dimensions. Internal consistency reliability of the scale was found to be satisfactory. There was a high level of association with relevant SF-36, GHQ-12 and HADS scores. CONCLUSIONS: The SQLS was completed within 5-10 minutes. It possesses internal reliability and construct validity, and promises to be a useful tool for the evaluation of new treatment regimes for people with schizophrenia.

Adolescent↗
PubMed1999

An evaluation of worker lead exposures and cleaning effectiveness during removal of deteriorated lead-based paint.

We evaluated worker lead exposures and cleaning effectiveness during initial cleanup of 19th-century buildings with highly deteriorated lead-based paint. Eighteen rooms of similar size and condition in two university-owned buildings were selected for a pilot project to compare three methods for removing loose paint, paint chips, and dust. The methods used were: dry scraping followed by dry sweeping (no engineering or work practice controls); wet scraping and high-efficiency particulate air (HEPA) vacuuming; and the latter method with the addition of a portable HEPA-filtered exhaust fan in the room providing about 40 air changes per hour. The final step for all methods was wet-mopping once with tri-sodium phosphate solution. During a single day 18 rooms were cleaned; each of three two-person work crews cleaned six rooms, two with each method. Air and surface samples were collected before, during, and after cleaning. All of the methods were potentially hazardous to workers: 44 percent of the method-based exposures (range: 5.0-360 micrograms/m3) and one of five full-shift exposures exceeded the OSHA PEL (range 9.4-110 micrograms/m3). Lowest worker exposures were during the wet scraping and vacuuming method (mean: 24 micrograms/m3). Providing general ventilation in rooms did not reduce worker exposures and appeared to increase them (mean: 73 micrograms/m3). Overall, the mean floor surface lead levels were reduced 50 percent after cleaning (from 2,600 to 1,300 micrograms/ft2), but the effectiveness of the three methods in reducing floor lead levels did not differ significantly. Overall, the method, mean paint lead concentration, pre-cleaning surface lead concentration, and work crew were significantly associated with the mean worker exposures during cleaning (p = 0.023), but not with the post-cleaning surface lead concentrations (p = 0.13).

Air Pollutants↗
PubMed1998

MHC-dependent and -independent activation of human nickel-specific CD8+ cytotoxic T cells from allergic donors.

T lymphocytes are critical effectors in the pathogenesis of contact hypersensitivity. Nickel is the most common contact sensitizer in humans and nickel-specific CD4+ T helper cells have been extensively characterized. Because recent observations have suggested the activation of CD8+ T cells in murine models of contact hypersensitivity, we investigated the existence of CD8+ hapten-specific T lymphocytes in patients with allergy to nickel. Nickel-specific T cell lines were generated from the peripheral blood of three allergic donors. The T cell lines were composed of a majority of CD4+ T cells, but CD8+ T cells were also present and their percentage increased with repeated in vitro stimulations. In addition to nickel-reactive helper T cell-0-type or helper T cell-2-type CD4+ T cell clones, CD8+ T cell clones could be derived from these cell lines and a total of 15 clones were further studied. Cytokine production was evaluated for 11 CD8+ T cell clones that were either cytotoxic T cell-0- or cytotoxic T cell-1-type clones. Additional effector functions were investigated on the complete panel of T cell clones. These CD8+ T cells did not only display hapten-specific proliferation, but also specific cytotoxic activities towards autologous EBV-B cells in the presence of nickel. Two different types of CD8+ T cells were characterized. Most of the clones lysed only autologous targets in the constant presence of nickel; however, one clone was able to lyse numerous targets in the presence of NiSO4, irrespective of the expression of either major histocompatibility complex class I or class II molecules. The characterization of nickel-specific cytotoxic CD8+ T cells with different requirements for nickel-specific target lysis, may have important implications in the development or in the control of human contact hypersensitivity reactions to nickel in vivo.

Blood Donors↗
PubMed1998

Selective in vivo stimulation of stress-activated protein kinase in different rat tissues by immobilization stress.

Stress activated protein kinases (SAPK) are key enzymes mediating the cellular response to stressful stimuli. While they are intensively studied in cultured cells, little is known about their physiological role in vivo, or relevance to pathological conditions. Therefore we examined the effect of various times of immobilization on c-Jun N-terminal protein kinase (JNK) activity in several rat stress responsive tissues and in a number of other locations. The abundance and relative distribution of JNK isoforms, the basal levels, time course and relative magnitude of stress induced JNK activity differed among tissues and regions of the brain of the same animal. JNK immunoreactive proteins were most abundant in the brain, especially in the hippocampus, hypothalamus and frontal cortex. Marked activation in response to immobilization stress was observed in adrenal medulla, adrenal cortex, aorta and hippocampus, less pronounced in locus coeruleus. JNK was not affected in superior cervical ganglia, pituitary, hypothalamus, frontal cortex and cerebellum. In adrenal medulla, the activation of JNK by single immobilization stress is correlated with increased transcription of stress-responsive genes, tyrosine hydroxylase and dopamine beta-hydroxylase. These data suggest a potential role of JNK signal transduction pathway in mediating the long term adaptation to stressful stimuli in vivo.

Animals↗
PubMed1996

Risk of low red or white blood cell count related to estimated benzene exposure in a rubberworker cohort (1940-1975)

This study evaluated the relationship between benzene exposure and low white blood cell (WBC) and red blood cell (RBC) counts. Hematologic screening data collected over a 35 year period at a rubber hydrochloride manufacturing plant were analyzed; an increased risk of leukemia had been demonstrated previously among workers at the plant [Infante et al. (1977).' Lancet 2:76-78; Rinsky et al. (1981): Am J Ind Med 2:217-45 (1987): NEJM 316:1044-1050/. Hematologic screening data were available for 657 of 1,037 (63.3%) individuals employed at the plant from 1939 through 1976. There was a total of 21. 710 blood test records (range per individual 1-354). The study utilized a case-control design and estimated benzene exposures using the job exposure matrix developed by Rinsky et al. (1987): NEJM 316:1044-1050]. The effects of benzene exposure in the 30, 90, and 180 days before the blood test date, as well as cumulative exposure up until the blood test date, were examined using conditional logistic regression. For WBCs there was a strong exposure response and all of the exposure metrics selected showed a significant relationship with low blood count. For RBCs there was a weak positive exposure-response, which was significant (p = 0.03) for one of the dose metrics. The finding of an exposure-response relationship in the range of exposures represented in this study, where the maximum daily benzene exposure estimate was 34 ppm, is consistent with findings of several animal studies demonstrating a decrease in peripheral lymphocyte counts at benzene exposures as low as 10 ppm, and a stronger effect of benzene exposure on lymphocytes (as reflected in total WBC count) than on red cells. There was no evidence for a threshold for the hematologic effects of benzene exposure, suggesting that even exposure to relatively low levels of benzene (e.g., <5 ppm) may result in hematologic suppression.

Benzene↗
PubMed1996

A new edge detector for gray volumetric data.

We propose a 3-D edge detector for gray voxel-based data, generalizing the well-known Sobel operator for 2-D images. Three differentiation operators are defined corresponding to the three principal directions (coordinate axes). Each operator computes the sum of the intensity differences between certain pairs of neighbors of a voxel corresponding to a principal direction. The proposed edge detector corresponds to the square root of the average of the squares of the three differentiation operators. Implementation of the proposed operator is given for biological images such as CAT and MRI scan data and an electron density map of a macromolecule.

Algorithms↗
PubMed1996

A silver tattoo of the nasal mucosa after silver nitrate cautery.

We report a silver tattoo of the nasal mucosa that occurred after silver nitrate cautery for nasal bleeding. This type of tattoo is a very rare potential mimic of melanoma and appears not to have been described before. It has similar features to an amalgam tattoo of the oral mucosa on histology and energy dispersive X-ray analysis (EDAX).

Aged↗
PubMed1995

Measuring health-related quality of life in persons with genital herpes.

A disease-specific measure was needed for use in an international clinical trial to evaluate an investigational drug for genital herpes. A new measure was developed initially in the UK and translated and adapted for use in France, Italy, Germany, Denmark, Spain and the USA. This paper describes the translation and adaptation of the USA measure. It also describes the assessment of internal consistency, reproducibility, content validity, and construct validity (convergent and discriminant) of the measure. Two outcome measures of the final genital herpes-specific measure were developed: (1) a 21-item symptoms subscale; and (2) a 20-item HRQOL subscale. Each measure was scored and analyzed separately; the psychometric testing discussed in this paper refers to the HRQOL subscale only. The internal consistency of the HRQOL subscale is high (r = 0.93), as is the reproducibility measured with a two week interval (r = 0.85). Convergent validity is moderate to high. (Fleming Self-Regard subscale, r = 0.48; SF-36 Social Functioning dimension r = 0.59; SF-36 Mental Health dimension r = 0.50). The number of herpes outbreaks in the past year was a significant predictor of scores on the HRQOL subscale (0-1 outbreaks, mean = 82.1; 2+ outbreaks, mean = 72.1, p = 0.058) suggesting discriminant validity. The measure is currently in a phase III clinical trial including anti-viral therapy where the question of responsiveness can be addressed.

Adult↗
PubMed1995

[Improved microbiological assay of heterocyclic aromatic amines in cooked food].

Heating of protein, especially muscle meat and meat extracts, can result in the formation of heterocyclic aromatic amines (HA) which are carcinogenic in animals. They are therefore unwelcome in human food. Here, an improved method for the microbiological assay of HA is reported; it makes use of the high mutagenic potency of HA in the Ames test and of the new Salmonella typhimurium strain YG1024 instead of strain TA98. The high sensitivity of the new strain is a consequence of its high acetyltransferase activity which results in a more efficient formation of genotoxic HA metabolites. The mutagenic activity of three selected HA in YG1024 is 10-20 times higher than that in TA98. This method can be used for the analysis of the HA content of food. A study of meat patties revealed significant differences in the mutagenic activity in the center and crust and of home-made and commercial patties; in both, the mutagenic activity was localized in the crust.

Amines↗
PubMed1995

Prostaglandin-H synthase mediated metabolism and mutagenic activation of 2-amino-3-methylimidazo [4,5-f] quinoline (IQ).

Prostaglandin-H synthase (PHS), a mammalian peroxidase of interest for the extrahepatic formation of reactive intermediates of carcinogens, catalyzes in vitro the metabolic activation of the mutagen and carcinogen 2-amino-3-methylimidazo-[4,5-f]quinoline (IQ). Incubation of 14C-labeled IQ with ram seminal vesicle microsomes (RSVM), a rich source of PHS, resulted in protein binding and generated products mutagenic in S. typhimurium YG1024. The mutagenic activity produced in IQ/PHS incubations was stable and extractable with ethyl acetate. Upon fractionation of such extracts by HPLC and subsequent analysis, two metabolites were identified as 2,2'-azo-bis-3-methylimidazo[4,5-f]quinoline (azo-IQ) and 3-methyl-2-nitro-imidazo[4,5-f]quinoline (nitro-IQ) confirmed by comparison of HPLC retention times, UV/VIS-, 1H-NMR-spectroscopy, and mass spectrometry of synthesized standards. Azo-IQ was obtained by chemical oxidation of IQ with meta-sodium periodate. It was the major metabolite in PHS incubations, but has not been detected in monooxygenase incubations. Azo-IQ, without metabolic activation, was much less mutagenic in S. typhimurium YG1024 (308 rev/nmol) than nitro-IQ and 3-methyl-2-nitroso-imidazo[4,5-f]quinoline (nitroso-IQ), two other S9-independent mutagens which have been synthesized by chemical oxidation of IQ with sodium nitrite. Nitro-IQ was formed only in trace amounts but due to its potent mutagenicity in S. typhimurium YG1024 (2 x 10(6) rev/nmol) it accounted for most of the mutagenic activity of the incubations. These data show that PHS-mediated in vitro metabolism of IQ results in its metabolic activation; thus PHS may contribute to the genotoxicity of IQ in extrahepatic tissues.

Animals↗
PubMed1995

Metabolic activation of heterocyclic aromatic amines catalyzed by human arylamine N-acetyltransferase isozymes (NAT1 and NAT2) expressed in Salmonella typhimurium.

Heterocyclic aromatic amines formed during the cooking of meat and meat-derived products can be activated to reactive metabolites which bind to DNA, induce mutations and cause tumors in animals. A principal route of metabolic activation is N-oxidation to hydroxylamines, and their subsequent activation by acetyltransferase-catalyzed O-acetylation. We have used mutagenicity assays to study O-acetylation of heterocyclic arylhydroxylamines by the two isozymes of human N-acetyltransferase, NAT1 and NAT2, expressed in Salmonella typhimurium. N-Acetylation was also examined, using an HPLC method. In addition, Salmonella strains with endogenous acetyltransferase and lacking this activating activity were used. Hydroxylamines of nine heterocyclic aromatic amines, IQ, isoIQ, MeIQ, MeIQx, NI, PhIP, Glu-P-1, Glu-P-2, and Trp-P-2 were generated in situ by rat liver S9 mix. The strains expressing human NAT1 and lacking acetyltransferase activity showing little or no ability to activate these substrates. The strains expressing human NAT2 and Salmonella acetyltransferase supported to different extents the activation of all the compounds except PhIP and Trp-P-2. N-Acetylation of IQ, MeIQx and PhIP was slow or not detectable. In conclusion, human NAT2 but not NAT1 can O-acetylate heterocyclic hydroxylamines. NAT2 probably plays a key role in the genotoxic effects of the above heterocyclic amines except for PhIP and Trp-P-2, which have NAT2-independent mutagenic activity.

Acetylation↗
PubMed1995

Can we prevent accidental injury to adolescents? A systematic review of the evidence.

OBJECTIVES: As part of the Department of Health strategy The Health of the Nation, a systematic review of published and unpublished literature relating to the effectiveness of interventions in reducing accidental injury in the population aged 15-24 years was carried out. METHODS: The literature was reviewed under the standard setting headings of road, work, home, and sports and leisure, and graded for quality of evidence and strength of recommendation using a scale published in the UK national epidemiologically based needs assessment programme. RESULTS: The most effective measures appear to be legislative and regulatory controls in road, sport, and workplace settings. Environmental engineering measures on the road and in sports have relatively low implementation costs and result in fewer injuries at all ages. There is little evidence that purely educational measures reduced injuries in the short term. Community based approaches may be effective in all age groups, and incentives to encourage safer behaviour hold promise but require further evaluation. The potential of multifactorial approaches seems greater than narrowly based linear approaches. CONCLUSIONS: Few interventions to reduce injury in adolescents have been rigorously evaluated using good quality randomised controlled trials, and where such evidence is available, fewer have been shown to be definitely worthwhile. Many studies relied on surrogate measures rather than actual injury rates, and substantial issues relating to the efficacy or implementation of preventive measures in adolescent and young adult populations remain unresolved.

Accident Prevention↗