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Biomedical subjects

M R Cook

Publications and source records attributed to M R Cook.

At least 19 recordsLinked to original sources

Melatonin and 6-OHMS in high-intensity magnetic fields.

We determined if all-night exposure to 60 Hz magnetic fields at an intensity well within the upper range of occupational exposures (resultant intensity = 127.3 microTesla [muT]) resulted in suppression of melatonin or its major metabolite 6-hydroxymelatonin-sulfate (6-OHMS) in the first-void morning urine of 24 healthy male volunteers. Measures collected after continuous and intermittent magnetic field exposure test conditions were compared to similar measures collected after an equivalent no-exposure control condition. Urinary concentrations of melatonin and 6-OHMS did not differ as a function of type of magnetic field exposure, nor did they differ between field exposure and control conditions. These results demonstrate that the nocturnal secretion and metabolism of melatonin are not altered in humans by field exposure at an intensity over 600 times higher than that typically encountered in the home.

Adult↗

All-night exposure to EMF does not alter urinary melatonin, 6-OHMS or immune measures in older men and women.

Healthy men (n = 22) and women (n = 24), 40-60 years of age, were exposed all-night (23:00-07:00 hr) to 60-Hz magnetic fields at an intensity (resultant flux density = 28.3 microTesla [microT]) well within the occupational-exposure range, or sham exposed under equivalent, counter-balanced, no-exposure ( < or = 0.2 microT) control conditions. Concentrations of melatonin, and the major metabolite of melatonin, 6-hydroxymelatonin-sulfate (6-OHMS), in first-void morning urine were not altered in either gender by exposure to the magnetic field, compared to control conditions. Statistical analysis also failed to reveal any evidence for exposure-related alterations in blood concentrations of multiple hematologic and immune system parameters (CD3, CD4, CD8, natural killer [NK] cells). The present results replicate and extend earlier negative findings based on the exposure of young men to power-frequency magnetic fields.

Adult↗

Examination of the melatonin hypothesis in women exposed at night to EMF or bright light.

It has been hypothesized that the increased incidence of breast cancer in industrial societies is related to greater exposure to power-frequency electric and magnetic fields (EMF) and/or the presence of high levels of light at night (LAN). EMF and LAN are said to reduce circulating levels of the hormone melatonin which, in turn, allows estrogen levels to rise and stimulate the turnover of breast epithelial stem cells and increase the risk for malignant transformation. Three laboratory-based studies, in which a total of 53 healthy young women were exposed at night to EMF or to LAN under controlled exposure conditions, were performed to determine whether such exposures reduce melatonin and are associated with further alterations in estrogen. All-night exposure to industrial-strength magnetic fields (60 Hz, 28.3 microT) had no effect on the blood levels of melatonin or estradiol. In contrast, nocturnal melatonin levels were profoundly suppressed, and the time of peak concentration was significantly delayed in women exposed to LAN, regardless of whether they were in the follicular or luteal phase of the menstrual cycle. These changes, however, were not associated with alterations in point-for-point matching measures of estradiol. Women who chronically secrete high or low amounts of melatonin each night (area-under-curve range: 86-1,296 pg/mL) also did not differ in their blood levels of estradiol. Taken together, these results are consistent with a growing body of evidence which generally suggests that environmental EMF exposure has little or no effect on the parameters measured in this report.

Adult↗

Side effects of low-dose pyridostigmine bromide are not related to cholinesterase inhibition.

BACKGROUND: Pretreatment with pyridostigmine bromide (PB) has become part of standard military procedures for protection against the effects of possible chemical warfare attack. The purpose of the work reported here was to quantify the type, intensity and frequency of side effects of low-dose PB, and to examine factors that predict the intensity and frequency of side effects. METHOD: A double-blind, cross-over, placebo (PL)-controlled design was used. Of the 67 subjects, 33 received 30 mg PB every 8 h for 13 doses, and 34 received 60 mg on the same schedule. Order of PB and PL administration was counterbalanced. RESULTS: Overall, side effects were mild, even at the 60-mg dose level. More side effects were reported when volunteers were taking PB than when they were taking placebo. Women reported more symptoms than men. Neither cholinesterase inhibition nor plasma levels of PB predicted side effect scores during the PB week; the best predictor of side effect scores during the PB week was side effect scores during the PL week. CONCLUSION: PB is well tolerated by healthy young people, even when twice the recommended military dose is administered.

Adolescent↗

Nocturnal magnetic field exposure: gender-specific effects on heart rate variability and sleep.

OBJECTIVE: To determine if controlled exposure to power-frequency magnetic fields alters heart rate variability (HRV) and polysomnographic endpoints in healthy men (n=22) and women (n=24), 40-60 years of age. METHODS: A randomized, double-blind, crossover design was used. Study endpoints collected during all-night exposure to 60 Hz magnetic fields at an occupational intensity (resultant flux density=28.3 microTesla, microT) were compared to similar endpoints obtained under equivalent, counterbalanced, no-exposure (< or =0.2 microT) control conditions. RESULTS: Older men, but not women, exposed to the magnetic fields showed power reductions in the LF band of the HRV frequency spectrum, which is associated with sympathetically-mediated blood pressure and thermoregulatory control (P<0.04). Older women, but not men, exposed to the fields showed a pattern of disrupted sleep, with reductions in the duration of REM sleep (P=0.03), and strong trends for reductions in sleep efficiency (P=0.06) and total sleep time (P=0.06). CONCLUSIONS: The gender-specific effects seen here with older volunteers replicate the results of previous exposure studies with younger men and women.

Adult↗

Brain frequency magnetic fields alter cardiac autonomic control mechanisms.

OBJECTIVE: Heart rate variability (HRV) is a noninvasive indicator of sympathetic and vagal cardiovascular control known to be tightly correlated with sleep stages. Recent studies indicate that HRV in humans is altered by nocturnal exposure to power-frequency (60 Hz) magnetic fields. Given the central origin of autonomic cardiac control, we determined if field exposure in the beta(1) EEG/MEG frequency range was a more effective stimulus for HRV alteration than 60 Hz fields, and explored the mechanisms involved. METHODS: Healthy young men were exposed (n=9) overnight to an intermittent magnetic field (16 Hz, 28.3 microTesla, microT), or sham exposed (n=9), under blind test conditions in a laboratory exposure facility. RESULTS: Field exposure was associated (P<0.05) with reduced power in the low band of the HRV frequency spectrum, and with decreases in mean heart rate. Analysis of the timing of the R waves surrounding each on-off transition of the intermittent field revealed no evidence for a direct effect on the cardiac pacemaker. CONCLUSIONS: Magnetic field exposure in the EEG/MEG beta(1) frequency range alters HRV via a CNS effect. Phase-resetting experiments rule out a direct effect on the cardiac pacemaker. Biophysical calculations of the intensity of the electric fields induced in brain versus heart under the present exposure conditions are also consistent with and support a central rather than a peripheral site of action.

Adult↗

Multi-night exposure to 60 Hz magnetic fields: effects on melatonin and its enzymatic metabolite.

Magnetic field-induced suppression of nocturnal melatonin in humans has been reported in occupational and residential studies, but not in laboratory-based exposure studies. The present study examined whether this contrasting pattern of results might be related to associated differences in exposure duration or to field-induced measurement instability over time. Thirty healthy young men were evaluated using a randomized, double-blind test protocol. Statistical analysis indicated that 4 consecutive nights of exposure to power-frequency magnetic fields at occupational intensity (resultant flux density = 28.3 microtesla, muT, [283 milligauss, mG]) had no differential effect on concentrations of melatonin or its major enzymatic metabolite (6-hydroxymelatonin sulfate, 6-OHMS) in daily morning urine samples, compared to equivalent no-exposure sham control conditions. The consistency of intra-individual urinary measurements over the 4 test nights also was quite high (P < 0.01) in the sham control condition. In contrast, repeated nightly exposure to the magnetic field was associated with reduced consistency. Morning urinary measures obtained after exposure on night 4 differed (P < 0.01) from similar measures obtained after the second and third exposure night. Thus, while the overall results of this study do not support the melatonin hypothesis, there is some suggestion of a possible cumulative effect of magnetic field exposure on the stability of individual melatonin measurements over time. Additional research with longer periods of controlled exposure may be warranted.

Adolescent↗

Morning urinary assessment of nocturnal melatonin secretion in older women.

We evaluated the feasibility of using morning urine samples in epidemiological studies aimed at clarifying the relationship between nocturnal melatonin levels and breast cancer risk. Initially, a laboratory-based study of 29 women (40- 70 yr old) was performed to examine the correlation between plasma melatonin levels in hourly nocturnal blood samples and both melatonin and its major enzymatic metabolite, 6-hydroxymelatonin-sulfate (6-OHMS) in morning urine samples. In a companion field study, morning urine samples were collected from 203 healthy women to assess similarities and differences in laboratory versus field measures. Taken together, our results indicate: 1) levels of melatonin and of creatinine-corrected 6-OHMS in the first morning void urine are strongly correlated with total nocturnal plasma melatonin output (P < 0.001) and also with peak nocturnal melatonin values (P < 0.001); 2) similar ranges for 6-OHMS were found in the laboratory and the field; and 3) neither menopausal status nor hormonal replacement therapy altered 6-OHMS values in morning void urine. The inclusion of morning urine samples in epidemiological studies of cancer could allow cost-effective, widespread testing of the role played by melatonin in human health and disease.

Adult↗

Cardiac autonomic control mechanisms in power-frequency magnetic fields: a multistudy analysis.

Heart rate variability (HRV), a noninvasive indicator of autonomic control of cardiac activity, is predictive of long-term cardiac morbidity and mortality. Epidemiologic research suggests that occupational exposure to power-frequency magnetic fields may be associated with autonomically mediated cardiac mortality. Results from our laboratory studies of humans exposed to 60-Hz magnetic fields overnight, however, are inconsistent. HRV is altered in some studies but not others. To clarify this, the pooled data from seven studies involving 172 men were analyzed to test specific hypotheses concerning this inconsistency. After analysis, we excluded a) measurement drift or instability over time because HRV was stable under sham-exposed conditions across all studies; b) inadequate statistical power or failure to maintain double-blind controls; c) differences in field intensity (28.3 vs. 127.3 microT) or exposure pattern (intermittent versus continuous) as main effects; or d) the inclusion of individuals sensitive to magnetic field exposure in some studies but not others. Four separate analytic techniques failed to identify a valid subpopulation of sensitive individuals. In some studies, however, hourly blood samples were collected using an indwelling venous catheter. HRV alterations occurred during intermittent exposure in these studies (p < 0.05) but not in similar studies without blood sampling. This result suggests a field interaction with modest arousal or disturbance. Because HRV is tightly coupled to electroencephalographic activity during sleep, these results are physiologically plausible and suggest that HRV alterations during exposure to magnetic fields may occur when accompanied by increases in physiologic arousal, stress, or sleep disturbance.

Adolescent↗

Exposure to strong ELF magnetic fields does not alter cardiac autonomic control mechanisms.

Clinical and epidemiological studies attest that alterations in heart rate variability (HRV) are predictive of specific types of cardiovascular morbidity and mortality in otherwise healthy persons. Recent reports also suggest that changes in HRV may be associated with exposure to intermittent magnetic fields (60 Hz, 28.3 microT) in the laboratory and that mortality is increased in cardiac disease categories related to altered HRV for utility workers whose jobs involve longer exposure to elevated magnetic fields. This study combined three approaches to learn more about the specific exposure circumstances under which changes in HRV occur. First, cardiac autonomic control, as indexed by HRV spectral analysis measures, was measured in 24 men during exposure to a much higher intensity field than any previously examined (resultant flux density = 127.3 microT [1273 milliGauss, mG]). Second, HRV measures from the same individual were compared across three relevant test conditions: intermittent and continuous field exposure and during a no-exposure, control condition. Third, electrocardiographic data were analyzed to determine if the precise timing of when the magnetic field switched on or off in relation to the cardiac cycle results in phase-resetting of the human cardiac rhythm. HRV measures were not altered by either field exposure condition compared to the control condition, and no evidence for a phase-resetting mechanism was found. Further research is needed to resolve the differences between the present and the earlier laboratory-based studies of HRV and to determine if cardiac rhythm disturbances are associated with exposure to the more complex magnetic fields found in the man-made environment.

Adult↗

Heart rate variability and physiological arousal in men exposed to 60 Hz magnetic fields.

In previous research, intermittent exposure to sinusoidal 60 Hz magnetic fields at a resultant flux density of 28.3 microT was found to alter heart rate variability (HRV) in men during night sleep. When the 24 men in the present study were exposed under similar conditions, HRV was not altered. The previous studies included the hourly collection of blood samples via an indwelling venous catheter, while the present study did not. This may account for the observed differences in results. Further research is needed to determine if field exposure interacts with physiological arousal mechanisms to alter autonomic nervous system control over cardiac rhythms.

Adolescent↗

Test facility for human exposure to AC and DC magnetic fields.

For more than a decade, Midwest Research Institute (MRI) has investigated the effects of exposure to 60 Hz electric and magnetic fields (EMF) on human physiology, performance, and biochemistry. This accumulated experience, new research directions, and limited resources made it important to design more comprehensive and operationally cost-effective exposure facilities. Here we describe the new, integrated laboratory exposure test facilities recently constructed at MRI and present data on relevant characteristics of the exposure systems. Concentric coil systems were developed to generate uniform magnetic fields within the three new exposure rooms, with rapid cancellation of the field to ambient levels in the rest of the laboratory. Control systems are fully automated, computer-based, and independent. These provide the operational flexibility needed to present fields of different magnitudes, frequencies, and polarization. The local geomagnetic field can be modulated and/or canceled, and both AC and DC fields can be presented in various combinations. Capabilities for conducting double-blind experiments with true active-sham exposure conditions were implemented using bifilar windings and applying current flow in the opposite direction for each wire in a pair. The new facilities provide a comprehensive capability for laboratory-based human research on the potential effects of exposure to AC and DC magnetic fields.

Automation↗

Human sleep in 60 Hz magnetic fields.

This report describes a double-blind, laboratory-based study of 24 healthy young men in which sufficient data were collected to examine the effects of intermittent versus continuous exposure to a 60 Hz, 28.3 microT magnetic field on multiple EEG measures of night sleep. Intermittent, but not continuous or sham exposure, was associated with less total sleep time, reduced sleep efficiency, increased time in Stage II sleep, and decreased REM sleep. Subjects exposed intermittently to the field also reported sleeping less well and feeling less rested in the morning than subjects in the other two groups. All observed effects were significant at P < or = .04 or less. The public health relevance of these results cannot be assessed as yet. Poor sleep quality, however, can have a detrimental influence on worker safety and performance, and has been associated with decrements in memory and learning processes. Additional research appears warranted.

Adolescent↗

Human exposure to 60-Hz magnetic fields: neurophysiological effects.

The neurophysiological effects of exposure to power-frequency magnetic fields at two occupationally-relevant intensities were evaluated in a single-blind study with 18 male and 18 female volunteers. Auditory brainstem (BAEP) and somatosensory (SEP) evoked potentials were recorded before, during and after field exposure (duration = 45 min, frequency = 60 Hz, field intensities = 14.1 or 28.3 microtesla, microT), or an equivalent sham-exposure control period. Visual event-related potentials (VEP) to pattern reversal stimuli were also recorded before and after the exposure period. Field exposure had no differential effects on the BAEP, the VEP, or on SEP measures of central conduction time. Men and women showed a similar lack of sensitivity to exposure. The present results do not support the mechanistic hypothesis that the transmission of sensory information to appropriate cortical centers is delayed or distorted by exposure to power-frequency magnetic fields at occupational intensities.

Adolescent↗

Self-report of circadian type reflects the phase of the melatonin rhythm.

This study examined the relationship between circadian rhythm characteristics of the pineal hormone melatonin and individual differences in circadian type and mood. 95 healthy young men and 22 women were assessed each hour (00:00-07:00 h) for blood levels of melatonin throughout one night in the laboratory. Each subject was assessed for circadian type (morning, afternoon, or evening type) and morning mood (PANAS). Circadian type was strongly related to the melatonin acrophase but not to amplitude or time of year of assessment. Also, morning types evidenced a more rapid decline in melatonin levels after the peak than did evening types. Evening types were younger than were morning types. Female morning types reported more positive affect upon waking than did female afternoon or evening types. Males showed no such discrimination. Age was related to both melatonin acrophase and circadian type but did not explain the relationship between them. The results replicate and extend findings on circadian type and psychological and physiological variables.

Adolescent↗

Coping in real time: using Ecological Momentary Assessment techniques to assess coping with the urge to smoke.

Coping is important for success at smoking cessation, yet little is known about the natural history of coping with urges to smoke during a cessation attempt. In this study, Ecological Momentary Assessment (EMA) methods were used to gather real-time quantitative and qualitative data. For 3 consecutive days during their first 10 days of smoking cessation, 36 participants used tape recorders and palm-top computers to record details of 389 coping episodes, during which they employed 1,047 coping responses. An average of 3.6 coping episodes per day and an average of 2.7 coping responses per episode were reported. Sixty-seven percent of the responses were behavioral and 33% were cognitive. Gender, location of the episode, nicotine dependence, and quitting history were associated with the use of specific strategies. Results indicate that EMA methods and instruments are feasible for measuring coping responses.

Adaptation, Psychological↗

Prediction of nocturnal plasma melatonin from morning urinary measures.

A growing literature indicates that blood levels of the hormone melatonin may have important implications for human health and well-being. Melatonin is synthesized and released into the general circulation at night, however, and it is seldom feasible to draw blood samples at night in epidemiological studies. There is some evidence that levels of urinary melatonin and of 6-sulfatoxymelatonin (aMT6s), the major metabolite of melatonin, accurately reflect nocturnal plasma melatonin. If this is the case, urinary assays could be powerful tools for epidemiological studies. A laboratory-based study was performed to examine the relationships between nocturnal plasma melatonin, morning urinary melatonin, and morning urinary aMT6s levels in 78 men. The relationship between total nocturnal plasma melatonin and both urinary aMT6s corrected for creatinine and urinary melatonin is significant. Combining the two urinary measures accounts for 72% of the variance in total plasma melatonin. Peak nocturnal plasma melatonin also was significantly related to urinary melatonin and to aMT6s. The urinary measures show good sensitivity and specificity in identifying individual differences in nocturnal plasma melatonin levels. These results support the inclusion of morning urine samples to assess the contribution of the hormone melatonin in occupational or residential studies involving healthy, young men.

Adolescent↗

Nocturnal exposure to intermittent 60 Hz magnetic fields alters human cardiac rhythm.

Heart rate variability (HRV) results from the action of neuronal and cardiovascular reflexes, including those involved in the control of temperature, blood pressure and respiration. Quantitative spectral analyses of alterations in HRV using the digital Fourier transform technique provide useful in vivo indicators of beat-to-beat variations in sympathetic and parasympathetic nerve activity. Recently, decreases in HRV have been shown to have clinical value in the prediction of cardiovascular morbidity and mortality. While previous studies have shown that exposure to power-frequency electric and magnetic fields alters mean heart rate, the studies reported here are the first to examine effects of exposure on HRV. This report describes three double-blind studies involving a total of 77 human volunteers. In the first two studies, nocturnal exposure to an intermittent, circularly polarized magnetic field at 200 mG significantly reduced HRV in the spectral band associated with temperature and blood pressure control mechanisms (P = 0.035 and P = 0.02), and increased variability in the spectral band associated with respiration (P = 0.06 and P = 0.008). In the third study the field was presented continuously rather than intermittently, and no significant effects on HRV were found. The changes seen as a function of intermittent magnetic field exposure are similar, but not identical, to those reported as predictive of cardiovascular morbidity and mortality. Furthermore, the changes resemble those reported during stage II sleep. Further research will be required to determine whether exposure to magnetic fields alters stage II sleep and to define further the anatomical structures where field-related interactions between magnetic fields and human physiology should be sought.

Adolescent↗