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Biomedical subjects

M Clayton

Publications and source records attributed to M Clayton.

At least 19 recordsLinked to original sources
PubMed2003

The development of referral guidelines for dentists referring children for extractions under general anaesthesia.

OBJECTIVE: To develop a set of guidelines for referral of children for simple extractions under general anaesthesia and to determine if services providing general anaesthetic extractions comply with the guidelines. DESIGN: The guidelines were developed with reference to published literature and experts in the field. Patient's records were used to determine the compliance with the guidelines. SETTING: Community dental services in the North West of England in 2000. SUBJECTS: One hundred and ninety six sets of patient records of children attending to have teeth extracted under general anaesthesia were studied. RESULTS: The mean age of the 196 children was 6.8 years (SD = 2.5 years) and ranged from 2.7 to 15.8 years. Caries was the prime reason for extractions (182; 93b). Of the 196 children who received a general anaesthetic, 103 (53%) dentists had complied with the general anaesthetic referral guidelines whilst 93 (47%) had not. There was wide variation in compliance across 11 trusts in the North West of England. The lowest compliance was 25% and the highest 93%. CONCLUSION: This study has demonstrated that there can be considerable agreement amongst a group of experts on what constitutes clear justification for extracting teeth under general anaesthesia. However there can be marked variation in compliance with these guidelines.

Adolescent↗
PubMed2001

Application of standardized quality control procedures to open-path Fourier transform infrared data collected at a concentrated swine production facility.

Open-path Fourier transform infrared (OP/FT-IR) spectrometry was used to measure the concentrations of ammonia, methane, and other atmospheric gases at a concentrated swine production facility. A total of 2200 OP/FT-IR spectra were acquired along nine different monitoring paths during an 8-day period between January 11 and 22, 1999. Standardized quality control (QC) procedures were applied to the archived OP/FT-IR spectra to verify that the instrument was set up and operating properly during the field study and to identify outliers in the concentration data. These QC procedures included measuring the random baseline noise, the signal strength, and the relative single-beam intensity in selected wavenumber regions; inspecting the archived spectra for wavenumber shifts, changes in resolution, and evidence of detector saturation; and examining time series plots of the target gas concentrations and the uncertainty values reported by the classical least-squares (CLS) analysis. Application of these QC procedures to the archived spectra identified 252 potential outliers. After a careful review of the original spectra, 41 of the 252 suspected outliers were designated as actual outliers. Of the QC criteria used during this study, the uncertainty values reported by the CLS analysis were the most reliable indicators of actual outliers.

Air Pollutants↗
PubMed2000

Consent in children: legal and ethical issues.

Children's wishes are often not respected. The law does not support children's involvement in consent. Nurses can be influential in supporting patients during the process of consent. Decisions may be made based upon ethical principles, which tend not to respect individual rights.

Adult↗
PubMed1999

Development of a database management/analysis system for field research activities within a coordinated research project.

There are several ways a database/analysis system can assist a scientist engaged in field research. Specifically, it can assist the scientist with accurate data collection and more rigorous data analyses. The database management portion of this system allows accurate data collection and provides easy data entry through the use of forms. In addition, it can provide the scientist with structured methods of error checking data entry and checking for implausible values and false zeros. The system can also assist the scientist with the organization of the data and provide easy methods of sorting, grouping, and selecting data for analysis. Data can then be exported to a data analysis program where the first step is data validation. A menu of analyses using examples from the coordinated research project (CRP) are demonstrated using statistical methods that test continuous and categorical data.

Analysis of Variance↗
PubMed1999

Hepatitis B virus transgenic mouse model of chronic liver disease.

A model for hepatitis B virus-associated chronic liver disease has been made using cloned hepatitis B virus DNA as a transgene in a severe combined immunodeficient host. These mice consistently support virus gene expression and replication. After adoptive transfer of unprimed, syngeneic splenocytes, these mice cleared virus from liver and serum, and developed chronic liver disease. This model will permit identification of the host and virus contributions to chronic liver disease in the absence of tolerance.

Adoptive Transfer↗
PubMed1999

Melatonin and the reduction or alleviation of stress.

In a double blind and placebo controlled study designed to investigate the effect of melatonin administration at 13:00 hr on menstrual characteristics, prolactin, and premenstrual syndrome-like symptoms during simulated eastward travel, it was noted that melatonin reduces or alleviates the stress associated with the simulated travel. Bright lights were utilized to simulate eastward movement across six time zones. Melatonin (10 mg) was given to healthy females for 5 consecutive days during the late follicular and early luteal phases of the menstrual cycle. Hourly blood samples, used for analysis of melatonin and prolactin levels, were obtained for 24 hr before entering the dose administration phase of the study and again on the last dose day. Volunteers also completed a profile of moods state questionnaire upon waking on each of 8 days which overlapped the in-house dose administration days. The placebo group showed a prolactin peak at 13:00 hr (dose time) on the last dose day/blood draw, while the melatonin group showed a prolactin peak at 15:00 hr. The prolactin peak at 13:00 hr is likely the result of stress, since stress is known to elicit the release of prolactin. The peak at 15:00 hr in the melatonin group was likely elicited by the administration of melatonin. Stress reduction in the melatonin group was supported by results from the profile of moods state questionnaire. The melatonin group consistently demonstrated scores indicative of less stress.

Adolescent↗
PubMed1997

Cellular kinetics of induction by oltipraz and its keto derivative of detoxication enzymes in human colon adenocarcinoma cells.

Oltipraz [5-(2-pyrazinyl)-4-methyl-1,2-dithiole-3-thione] is a synthetic dithiolethione with chemopreventive activity against carcinogen-induced neoplasia of liver, lung, and colon in several animal model systems. Protection from tumor formation is associated with elevation of Phase II enzymes, including glutathione (GSH) transferase and NAD(P)H:quinone oxidoreductase (DT-diaphorase) in experimental carcinogenesis models in vivo. To investigate the time and dose relationships of the pharmacological action of oltipraz and to develop a model for its investigation, a human colon adenocarcinoma HT29 cell line was primarily used. In this cell line, oltipraz resulted in increased activity of both GSH transferase and DT-diaphorase. At the maximum effective concentration (100 microM), the elevation of GSH transferase was 3-fold and that of DT-diaphorase was 2-fold. The optimal duration of oltipraz exposure to HT29 cells was 24 h, following which the peak in enzyme activity was observed at 24 h after removal of the drug, and activity had almost returned to control levels after 72 h in drug-free media. Steady-state mRNA levels for DT-diaphorase were observed to increase during the period of drug exposure and remained elevated, even as catalytic activities declined to control levels, suggesting additional mechanisms for control of the activity of this enzyme. More prolonged drug exposure was associated with less induction of the detoxication enzymes, prompting an investigation of the possible toxicity of oltipraz to these cells. Although the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay revealed inhibition of proliferation (IC50, 100 microM oltipraz), a clonogenic assay demonstrated no loss of clonogenicity. Oltipraz is known to be extensively metabolized in many species; two major metabolites include a 3-ketone (metabolite 2, M2) and a molecular rearrangement to a pyrrolopyrazine derivative (metabolite 3, M3), numerous conjugates of which are formed in vivo. To investigate the potential cause of the lag in response, we synthesized two major oltipraz metabolites (M2 and M3) and tested their efficacy in enzyme induction. The activity of DT-diaphorase was induced similarly by both oltipraz and M2 (2.6- versus 2.8-fold baseline) at 100 microM, whereas M3 was inactive at all concentrations. M2 also resulted in a 5.8-fold elevation of steady-state DT-diaphorase mRNA levels. Both enzyme activity and steady-state mRNA peaked at 24 h as with the parent compound. Thus, the oxidative desulfuration of oltipraz results in the formation of an active metabolite, but this process is not rate limiting for the induction of detoxicating enzymes. These data support the use of intermittent schedules in oltipraz in clinical trials of chemoprevention because of evidence of attenuation of response. The metabolite M2, but not M3, is as active as the parent compound and may be considered for clinical development in its own right.

Adenocarcinoma↗
PubMed1995

Apoptosis in human adenocarcinoma HT29 cells induced by exposure to hypoxia.

BACKGROUND: Recent evidence indicates that programmed cell death or apoptosis may be an important mechanism for the lethality of cancer chemotherapy drugs in tumor cells. Apoptosis may be induced in tumor cells by a number of physical stresses, including radiation, UV light, heat shock, and cold. In preliminary studies, we have found that exposure of cells to hypoxia rapidly induces the expression of several immediate early genes, including c-jun, jun-D, and c-fos, and of a bifunctional redox protein/endonuclease, Ref-1. PURPOSE: Our purpose was to determine if hypoxia-induced overexpression of the endonuclease was associated with altered DNA integrity and manifestations of apoptosis. METHODS: We examined cultured cells for the induction of apoptosis by electrophoresis and immunofluorescence techniques and related these findings to the induction of gene expression by hypoxia. RESULTS: We found that an 8-hour exposure of human adenocarcinoma HT29 cells to hypoxia (which results in only 14% loss of viability) induced internucleosomal DNA fragmentation beginning after 8 hours of hypoxia and before reoxygenation. Immunofluorescence of hypoxia-treated cells showed that apoptotic cells were detectable initially after 4 hours of hypoxia and reached a peak (31.3% of cells) at 12 hours after reoxygenation and that by 36 hours after reoxygenation all apoptotic cells had been eliminated from the population. Hypoxia-induced apoptosis was associated with a marked induction of c-myc messenger RNA (mRNA). We have previously shown that hypoxia is associated with ref-1 mRNA induction. While expression of c-myc declined with a time course similar to that of the disappearance of apoptotic cells, that of ref-1 remained elevated. Coincident with the decline of c-myc, we observed a late increase in the expression of bcl-2 beginning 24 hours after reoxygenation. CONCLUSIONS AND IMPLICATIONS: These results suggest a possible relationship between Ref-1 induction and the occurrence of apoptosis following a hypoxic exposure.

Adenocarcinoma↗
PubMed1994

Effects of hypoxia on detoxicating enzyme activity and expression in HT29 colon adenocarcinoma cells.

Resistance of hypoxic tumor cells to ionizing radiation and cytotoxic drugs has been attributed to changes in the reactivity and/or the half-times of reactive species in the altered redox environment. Exposure of eukaryotic cells to such hypoxic conditions results in the induction of the synthesis of several unrelated proteins. To investigate further the phenomenon of hypoxic cell resistance to cytotoxic drugs, we examined the effects of hypoxia on the expression of a group of enzymes involved in drug metabolism. Exposure of HT29 colon carcinoma cells to hypoxia resulted in a marked increase in the activity of DT-diaphorase and in glutathione content. The activity of glutathione transferase was not increased by this treatment. The response was proportional to the duration of hypoxia. After the cells were exposed to hypoxic conditions for 8 h, followed by restoration of an oxic environment, the elevation in enzyme activity and glutathione content reached a peak at 48 h (40 h after the restoration of an oxic environment) and returned to baseline at 72 h. Elevation of steady-state levels of DT-diaphorase and gamma-glutamylcysteine synthetase mRNA followed a similar time course, with > 10-fold increases over oxic cells at 24 h. The elevation of DT-diaphorase mRNA content was found to result both from transcriptional induction and from increased message stability. The magnitude and persistence of elevated detoxicating enzyme activity following a relatively short hypoxic exposure followed by reoxygenation suggest a novel potential mechanism of resistance to cytotoxic drugs in hypoxic tumors.

Adenocarcinoma↗
PubMed1994

Relationship of plasma epinephrine and circulating eosinophils to nocturnal asthma.

The mechanisms of nighttime airway obstruction are not fully established, but include circadian fluctuations in epinephrine and cortisol. To evaluate the relationship of circadian patterns in epinephrine and cortisol to nighttime airflow obstruction, 10 young adult asthma patients (ages 19 to 25 yr) were admitted to a hospital clinical research unit for a 3-day study during which plasma concentrations of epinephrine, cortisol, and histamine were determined along with white blood cell and eosinophil counts every 6 h (1600, 2200, 0400, and 1000 h). Six of the 10 patients experienced at least one episode of nocturnal asthma (defined by more than a 15% decrease in antemeridian (A.M.) to postmeridian (P.M.) FEV1 values). Plasma epinephrine levels (pg/ml) showed a circadian pattern, and the concentration at 2200 h was significantly (p = 0.039) different for the nocturnal and non-nocturnal asthma groups. Circulating eosinophil numbers were greater in subjects who had more frequent episodes of nocturnal asthma, and correlated with the frequency of nocturnal asthma (r = 0.732, p = 0.02, Spearman rank correlation) and average percent decrease in FEV1 (r = 0.667, p = 0.035). Plasma cortisol concentrations also showed circadian patterns, but no direct association with nocturnal asthma; plasma histamine concentrations showed no circadian patterns and no association with nocturnal asthma. Our findings indicate that changes in plasma epinephrine precede the development of nocturnal airway obstruction and contribute to the likelihood of nighttime airflow obstruction.

Adult↗
PubMed1994

Interaction of heat and hypoxia in modulating transcription of DT diaphorase in human colon adenocarcinoma cells.

To study the regulation of the human detoxicating enzyme DT diaphorase (DTD) under hypoxic conditions, we examined the effects of heat and hypoxia, and their interaction, on the steady-state levels of mRNA and DTD enzyme activity in human colon adenocarcinoma HT29 cells. We found that a 1-h heat treatment (42.5 degrees C) markedly increased the specific activity of DTD. Elevated enzyme activity was observed within 30 min, peaked at 6 h, and had almost returned to baseline by 36 h. The effect of hypoxia alone on DTD enzyme activity developed more slowly, with a maximal response at 24 h, and return to baseline at 72 h. The effect of a 1-h heat treatment was not inhibited by subsequent hypoxic exposure for 8 h. The effect of hypoxia was also not inhibited by heat in any schedule. However, a 1-h exposure to heat during 8 h hypoxic exposure induced the transcriptional effects of heat treatment much earlier. Heat shock followed by hypoxic stress resulted in prolonged elevation of DTD activity similar to that observed with hypoxia alone. We found that DTD mRNA content was elevated with a time course concordant with that of the enzyme activity. These data suggest that hypoxia and heat shock induce expression of the DTD gene independently. The mechanism of heat effect on DTD gene expression was investigated. Gel retardation assays demonstrated the induction of a binding activity of heat-induced transcription factor(s) to heat shock elements following both heat and hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗