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M A Jackson

Publications and source records attributed to M A Jackson.

At least 19 recordsLinked to original sources
PubMed2001

Evidence from the waking electroencephalogram that short sleepers live under higher homeostatic sleep pressure than long sleepers.

We used the waking electroencephalogram to study the homeostatic sleep regulatory process in human short sleepers and long sleepers. After sleeping according to their habitual schedule, nine short sleepers (sleep duration < 6 h) and eight long sleepers (> 9 h) were recorded half-hourly during approximately 40 h of wakefulness in a constant routine protocol. Within the frequency range of 0.25-20.0 Hz, spectral power density in the 5.25-9.0 and 17.25-18.0 Hz ranges was higher in short sleepers than in long sleepers. In both groups, increasing time awake was associated with an increase of theta/low-frequency alpha activity (5.25-9.0 Hz), whose kinetics followed a saturating exponential function. The time constant did not differ between groups and was similar to the previously obtained time constant of the wake-dependent increase of slow-wave activity (0.75-4.5 Hz) in the sleep electroencephalogram. In addition, the time constant of the decrease of slow-wave activity during extended recovery sleep following the constant routine did not differ between groups. However, short sleepers showed an abiding enhancement of theta/low-frequency alpha activity during wakefulness after recovery sleep that was independent of the homeostatic process. It is concluded that, while the kinetics of the homeostatic process do not differ between the two groups, short sleepers live under and tolerate higher homeostatic sleep pressure than long sleepers. The homeostat-independent enhancement of theta/low-frequency alpha activity in the waking electroencephalogram in the short sleepers may be genetically determined or be the result of long-term adaptation to chronically short sleep.

Adult↗
PubMed2000

A review of the genetic and related effects of 1,3-butadiene in rodents and humans.

In this paper, the metabolism and genetic toxicity of 1,3-butadiene (BD) and its oxidative metabolites in humans and rodents is reviewed with attention to newer data that have been published since the latest evaluation of BD by the International Agency for Research on Cancer (IARC). The oxidative metabolism of BD in mice, rats and humans is compared with emphasis on the major pathways leading to the reactive intermediates 1,2-epoxy-3-butene (EB), 1,2:3, 4-diepoxybutane (DEB), and 3,4-epoxy-1,2-butanediol (EBdiol). Results from recent studies of DNA and hemoglobin adducts indicate that EBdiol may play a more significant role in the toxicity of BD than previously thought. All three metabolites are capable of reacting with macromolecules, such as DNA and hemoglobin, and have been shown to induce a variety of genotoxic effects in mice and rats as well as in human cells in vitro. DEB is clearly the most potent of these genotoxins followed by EB, which in turn is more potent than EBdiol. Studies of mutations in lacI and lacZ mice and of the Hprt mutational spectrum in rodents and humans show that mutations at G:C base pairs are critical events in the mutagenicity of BD. In-depth analyses of the mutational spectra induced by BD and/or its oxidative metabolites should help to clarify which metabolite(s) are associated with specific mutations in each animal species and which mutational events contribute to BD-induced carcinogenicity. While the quantitative relationship between exposure to BD, its genotoxicity, and the induction of cancer in occupationally exposed humans remains to be fully established, there is sufficient data currently available to demonstrate that 1,3-butadiene is a probable human carcinogen.

Air Pollutants, Occupational↗
PubMed2000

Neck dissection and ipsilateral radiotherapy in the management of cervical metastatic carcinoma from an unknown primary.

BACKGROUND: In a small proportion of patients presenting with metastases to cervical lymph nodes the primary cancer remains occult despite thorough evaluation. The present report examines patterns of failure and outcome following an initial treatment strategy directed principally at the clinically involved side of the neck. METHODS: From a prospectively compiled computerized database 38 patients were identified with metastatic squamous cell carcinoma from an occult primary site. These patients were evaluated with respect to initial treatment, subsequent detection of a primary tumour, neck recurrence and survival characteristics. RESULTS: Thirty-seven of 38 patients were treated with curative intent and all had neck dissection. Adjuvant radiotherapy was given to 34 of the 37 (90%; 32 postoperatively and two pre-operatively). Radiotherapy was directed at the ipsilateral neck alone in 24 patients while 10 received comprehensive treatment to both sides of the neck and potential occult primary sites. The rate of control of disease in the ipsilateral neck was 91% while the failure rate in the contralateral neck was 16% (six patients). A primary cancer was ultimately identified in five patients (13%). Disease-specific survival was 63% at 4 years. Clinical N3 stage, extracapsular tumour extension and involved surgical margins predicted for poorer survival on univariate analysis. Analysis using multiple risk factors found that only involved surgical margins predicted for treatment failure. CONCLUSIONS: Despite generally advanced disease at presentation, patients presenting with cervical metastasis from an unknown primary carcinoma have a reasonable survival expectation and aggressive treatment is warranted, but approximately half will develop recurrent disease. Careful follow-up is required if effective salvage treatment is to be instituted.

Aged↗
PubMed2000

Peripheral infusion of Diazemuls.

Diazemuls is a very powerful anxiolytic agent with sedating and anti-epileptogenic properties. Unfortunately, until now it has not been possible to give Diazemuls accurately and safely as an infusion. A new delivery system ensures that, as an infusion, this drug is potentially very effective in treating patients with terminal agitation, status epilepticus, drug and alcohol withdrawal.

Adult↗
PubMed2000

Hemodialysis-induced hypoglycemia in diabetic patients.

BACKGROUND: The authors have previously reported asymptomatic hypoglycemia in non-diabetic patients on hemodialysis. The present study was designed to assess the effect of hemodialysis on plasma glucose, glucagon, cortisol and catecholamines in diabetic patients. METHODS: Eighteen diabetic patients with chronic renal failure were hemodialyzed using a glucose-free dialysis fluid. They did not take any medication prior to dialysis and were asked not to eat during the first hour on hemodialysis. Blood and dialysate were sampled at regular intervals during the first hour of dialysis for analysis. RESULTS: Plasma glucose fell below 4.0 mmol/l (72 mg/dl) in 7 of the 18 patients, below 3.5 mmol/l (63 mg/dl) in 3 and below 3.0 mmol/l (54 mg/dl) in one. The lowest recorded value was 2.8 mmol/l (50 mg/dl). The mean glucose loss in the waste dialysate was 9.2 g/h. In none of the group of 7 patients whose plasma glucose fell below 4.0 mmol/l (72 mg/dl) did symptoms of hypoglycemia occur. When 6 patients from this group were subsequently dialyzed with a dialysis fluid containing 5.5 mmol/l (100 mg/dl) glucose, their plasma glucose became stabilized within the fasting reference range. There were no significant hormonal changes during the dialysis or between non-hypoglycemic and hypoglycemic patients. CONCLUSIONS: Patients undergoing hemodialysis may become hypoglycemic and not be aware of it. There is no hormonal imbalance causing the hypoglycemia and the hormonal response to the hypoglycemia is blunted. Patients with an initial plasma glucose of 5.5 mmol/l (100 mg/dl) or less who are hemodialyzed and who do not eat during dialysis may be particularly at risk, especially if they are on insulin or taking glucose-lowering medication. These should be dialyzed with a dialysis fluid containing at least 5.5 mmol/l (100 mg/dl) glucose.

Blood Glucose↗
PubMed2000

Refinement of regions with allelic loss on chromosome 18p11.2 and 18q12.2 in esophageal squamous cell carcinoma.

Esophageal cancer ranks among the 10 most common cancers worldwide and is almost invariably fatal. The detailed genetic repertoire involved in esophageal carcinogenesis has not been defined. We have shown previously that the esophageal squamous cell carcinoma genome exhibits a frequent loss of heterozygosity (LOH) in the pericentromeric region of chromosome 18. To construct a fine deletion map, we screened 76 new samples composed of microdissected esophageal squamous cell carcinoma and matched morphologically normal epithelial cells using closely spaced markers. Maximal LOH frequency (54%) was displayed by D18S542 on 18p11.2. The pattern of LOH in selected patients indicated that the short region of overlap extends 3 cM on either side of D18S542. On the long arm of chromosome 18, the highest frequency of allelic loss (42%) was detected by D18S978 on 18q12.2-q21.1. This analysis revealed a short region of overlap of approximately 0.8 cM. These findings further implicate unreported tumor suppressor genes encoded by 18p11.2 and 18q12.2 in esophageal squamous cell carcinogenesis and they indicate a refinement of their map location.

Adult↗
PubMed1999

A survey of EPA/OPP and open literature on selected pesticide chemicals. II. Mutagenicity and carcinogenicity of selected chloroacetanilides and related compounds.

With this effort, we continue our examination of data on selected pesticide chemicals and their related analogues that have been presented to the U.S. Environmental Protection Agency's (USEPA's) Office of Pesticide Programs (OPP). This report focuses on a group of selected chloroacetanilides and a few related compounds. As part of the registration process for pesticidal chemicals, interested parties (registrants) must submit toxicity information to support the registration including both mutagenicity and carcinogenicity data. Although this information is available to the public via Freedom of Information (FOI) requests to the OPP, publication in the scientific literature allows greater dissemination and examination of the data. For this Special Issue, graphic profiles have been prepared of the mutagenicity and carcinogenicity data available in the submissions to OPP. Also, a discussion is presented about how toxicity data are used to help establish tolerances (limits of pesticide residues in foods). The mutagenicity results submitted by registrants are supplemented by data on these chemicals from the open literature to provide a full perspective of their genetic toxicology. The group of chloroacetanilides reviewed here display a consistent pattern of mutagenic activity, probably mediated via metabolites. This mutagenic activity is a mechanistically plausible factor in the development of tumors seen in experimental animals exposed to this class of chemicals.

Acetamides↗
PubMed1999

Genetic toxicology data in the evaluation of potential human environmental carcinogens.

In 1969, the International Agency for Research on Cancer (IARC) initiated the Monographs Programme to evaluate the carcinogenic risk of chemicals to humans. Results from short-term mutagenicity tests were first included in the IARC Monographs in the mid-1970s based on the observation that most carcinogens are also mutagens, although not all mutagens are carcinogens. Experimental evidence at that time showed a strong correlation between mutagenicity and carcinogenicity and indicated that short-term mutagenicity tests are useful for predicting carcinogenicity. Although the strength of these correlations has diminished over the past 20 years with the identification of putative nongenotoxic carcinogens, such tests provide vital information for identifying potential human carcinogens and understanding mechanisms of carcinogenesis. The short-term test results for agents compiled in the EPA/IARC Genetic Activity Profile (GAP) database over nearly 15 years are summarized and reviewed here with regard to their IARC carcinogenicity classifications. The evidence of mutagenicity or nonmutagenicity based on a 'defining set' of test results from three genetic endpoints (gene mutation, chromosomal aberrations, and aneuploidy) is examined. Recommendations are made for assessing chemicals based on the strength of evidence from short-term tests, and the implications of this approach in identifying mutational mechanisms of carcinogenesis are discussed. The role of short-term test data in influencing the overall classification of specific compounds in recent Monograph volumes is discussed, particularly with reference to studies in human populations. Ethylene oxide is cited as an example.

Animals↗
PubMed1999

Clinical utility of polymerase chain reaction testing for enteroviral meningitis.

BACKGROUND: During summer enteroviral meningitis is a common cause of febrile illness in children, who are typically hospitalized for 2 to 3 days if bacterial infection is suspected. It has been hypothesized that a sensitive polymerase chain reaction (PCR) assay could quickly confirm the diagnosis and subsequently decrease hospitalization costs. However, to have maximum impact results should be available within 24 h. This necessitates daily assays on small numbers of samples. METHODS: We examined the clinical utility of a PCR assay during two summers, comparing length of stay and charges. Only during the second summer were results reported to clinicians. Case controls were patients with negative PCR assay results but uncomplicated, presumed viral infections. We determined the cost per case identified with and without pleocytosis as a screen for PCR testing. RESULTS: During the first summer 25% (5/20) of patients with positive PCR assay results remained hospitalized for >2 days. During the second summer 10.2% (6 of 59) of children with positive enteroviral PCR assay results but 37.9% (25 of 66) of case controls remained hospitalized for >2 days. The mean length of hospitalization was significantly (P < 0.05) shorter for patients with positive PCR test results than for case controls. The material cost was approximately $238 per case identified. CONCLUSIONS: PCR testing has clinical utility for diagnosis of enteroviral meningitis. Although the demands for daily testing make the test expensive, it appears to be cost-effective with savings related to shorter hospital stays.

Case-Control Studies↗
PubMed1999

Two circadian rhythms in the human electroencephalogram during wakefulness.

The influence of the circadian pacemaker and of the duration of time awake on the electroencephalogram (EEG) was investigated in 19 humans during approximately 40 h of sustained wakefulness. Two circadian rhythms in spectral power density were educed. The first rhythm was centered in the theta band (4.25-8.0 Hz) and exhibited a minimum approximately 1 h after the onset of melatonin secretion. The second rhythm was centered in the high-frequency alpha band (10.25-13.0 Hz) and exhibited a minimum close to the body temperature minimum. The latter rhythm showed a close temporal association with the rhythms in subjective alertness, plasma melatonin, and body temperature. In addition, increasing time awake was associated with an increase of power density in the 0.25- to 9.0-Hz and 13.25- to 20. 0-Hz ranges. It is concluded that the waking EEG undergoes changes that can be attributed to circadian and homeostatic (i.e., sleep-wake dependent) processes. The distinct circadian variations of EEG activity in the theta band and in the high-frequency alpha band may represent electrophysiological correlates of different aspects of the circadian rhythm in arousal.

Adult↗
PubMed1999

Occult hypoglycemia caused by hemodialysis.

BACKGROUND: Previous studies have ignored hypoglycemia in patients undergoing hemodialysis. The fall in plasma glucose may not have been considered to be clinically relevant because the patients were asymptomatic. The present study was designed to assess the effect of hemodialysis on plasma glucose, insulin, glucagon, cortisol and catecholamines in non diabetic patients. METHODS: 21 non diabetic patients with chronic renal failure were hemodialyzed using a glucose-free dialysis fluid. They did not take any medication prior to dialysis and were asked not to eat during the first hour on hemodialysis. Blood and dialysate fluid was sampled at regular intervals during the first hour of dialysis for analysis. RESULTS: Plasma glucose fell below 4.0 mmol/l (72 mg/dl) in 9 of the 21 patients, below 3.5 mmol/l (63 mg/dl) in 6 and below 3.0 mmol/l (54 mg/dl) in 3. The lowest recorded value was 2.1 mmol/l (38 mg/dl). The mode glucose loss in the waste dialysate fluid was 6 g/h. In the group of 9 patients whose plasma glucose fell below 4.0 mmol/l (72 mg/dl), no symptoms of hypoglycemia were shown but 4 of the 7 patients who felt very hungry and ate were in this group. When 7 patients from this group were subsequently dialysed with a dialysis fluid containing 5.5 mmol/l (100 mg/dl) glucose, their plasma glucose became stabilized within the fasting reference range. There were no significant hormonal changes during the dialysis or between euglycemic and hypoglycemic patients. CONCLUSIONS: Patients undergoing hemodialysis may become hypoglycemic and not be aware of it. There is no hormonal imbalance causing the hypoglycemia and the hormonal response to the hypoglycemia is blunted. Patients with an initial plasma glucose of 4.5 mmol/l (81 mg/dl) or less who are hemodialyzed and who do not eat during dialysis may be particularly at risk. They should be dialysed with a dialysis fluid containing at least 5.5 mmol/l (100 mg/dl) glucose.

Blood Glucose↗
PubMed1999

Short-term tests for defining mutagenic carcinogens.

The results of short-term tests for mutagenicity were first included in the IARC Monographs in the mid-1970s on the basis of the observation that most carcinogens are also mutagens, although not all mutagens are carcinogens. The experimental evidence at that time showed a strong correlation between mutagenicity and carcinogenicity and indicated that the short-term tests were useful for predicting carcinogenicity. Although the correlations have become weaker over the past 20 years, and with them the predictive value of short-term tests, such tests still provide vital information for identifying and understanding mechanisms involved in carcinogenicity. The results of short-term tests compiled in the US Environmental Protection Agency-IARC Genetic Activity Profile database over the past 12 years are summarized and reviewed here in relation to the classification of agents for carcinogenicity within the system used at IARC. The role of the information from short-term tests in making overall classifications of specific compounds in recent Monographs is discussed. The usefulness of data on three genetic end-points, gene mutation, chromosomal aberrations and aneuploidy, and the criteria for mutagenicity and lack of mutagenicity based on a 'defining set' of test results are examined. Recommendations are made for assessing chemicals on the basis of the strength of the evidence from short-term tests, and the implications of this approach for identifying putative mutational mechanisms of carcinogenicity are discussed.

Aneuploidy↗
PubMed1998

Inhibition of genotoxic effects of mammalian germ cell mutagens.

Germ cell mutagens are among the most important chemicals for which chemopreventive agents should be sought and mechanistically defined. These mutagens may include environmental chemicals as well as drugs. In this investigation, the literature was reviewed for substances antimutagenic (or anticlastogenic) to compounds identified as mutagens in at least two germ cell studies. A complete matrix of test results was prepared to identify commonly tested pairs of germ cell mutagens and antimutagens. The categories of antimutagens most tested included vitamins, fatty acids, thiols, tannins and other phenolics. The most frequently studied mutagens were benzo[a]pyrene, cyclophosphamide, mitomycin C, and bleomycin. Based on the availability of the most relevant data, the analysis presented here focused on in vivo tests, specifically on bone marrow cytogenetics. The results indicated that antimutagens commonly found in the diet or endogenously in the body effectively antagonized the cytogenetic damage induced in the bone marrow by most of the germ cell mutagens studied to date. Bone marrow micronucleus and chromosomal aberration assays, which detect systemically active mutagens, may be predictive of similar mitigating effects in germ cells. Test results from antimutagenicity studies in germ cells, though limited, were comparable to the results from studies in the mouse bone marrow micronucleus test.

Animals↗
PubMed1997

Dynamics of the human EEG during prolonged wakefulness: evidence for frequency-specific circadian and homeostatic influences.

The electroencephalogram (EEG) of nine healthy individuals was recorded at half-hourly intervals during approximately 40 h of sustained wakefulness in a constant routine protocol. EEG power density in the 0.75-9.0 Hz range exhibited a global increasing trend, and a local trough in the evening, centered approximately 6 h prior to the temperature minimum. The former could be attributed to a wake-dependent influence, and the latter to a circadian influence. Power density in the 9.25-12.0 Hz band showed a circadian modulation, the trough coinciding with the minimum of the endogenous rhythm of body temperature, whereas a wake-dependent influence was not evident. Power density in the 12.25-25.0 Hz range exhibited a wake-dependent increase, whereas a circadian modulation was absent. It is concluded that the circadian pacemaker and the wake-dependent (i.e. homeostatic) process affect the waking EEG in a frequency-specific manner.

Adult↗