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Biomedical subjects

Robert R Freedman

Publications and source records attributed to Robert R Freedman.

15 recordsLinked to original sources
PubMed2006

Cortical activation during menopausal hot flashes.

OBJECTIVE: To determine regions of brain activation associated with menopausal hot flashes and sweating. DESIGN: Controlled laboratory study. SETTING: University medical center. PATIENT(S): Symptomatic postmenopausal women and asymptomatic eumenorrheic women. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Brain activation measured by functional magnetic resonance imaging. RESULT(S): Significant (P<.001) areas of activation during hot flashes in symptomatic women included the insula and anterior cingulate cortex. Sweating in the eumenorrheic women was associated (P<.001) with activity in the anterior cingulate and superior frontal gyrus. CONCLUSION(S): Activation of the insular cortex is associated with the "rush of heat" described during menopausal hot flashes. Thermoregulation in humans appears to be represented in a distributed cortico-subcortical network rather than in a single localized structure.

Adult↗
PubMed2005

Hot flashes: behavioral treatments, mechanisms, and relation to sleep.

Hot flashes are the most common symptom of the climacteric and occur in about 75% of perimenopausal and postmenopausal women in Western societies. Although hot flashes accompany the withdrawal of estrogen at menopause, the decline in estrogen levels is not sufficient to explain their occurrence. Elevated sympathetic activation acting through central alpha(2)-adrenergic receptors contributes to the initiation of hot flashes, possibly by narrowing the thermoneutral zone in symptomatic women. Hot flashes are then triggered by small elevations in core body temperature acting within this narrowed zone. A relaxation-based method, paced respiration, has been shown in 3 controlled investigations to significantly reduce objectively measured hot flash occurrence by about 50% with no adverse effects. In 6 studies of physical exercise, however, investigators did not find positive effects on hot flashes, possibly because exercise raises core body temperature, thereby triggering hot flashes. Although many epidemiologic studies have found increased reports of sleep disturbance during the menopausal transition, recent laboratory investigations have not found this effect, nor have they found that hot flashes produce disturbed sleep. Therefore, sleep complaints in women at midlife should not routinely be attributed to hot flashes or to menopause.

Behavior Therapy↗
PubMed2005

Thermoregulatory effects of 3,4-methylenedioxymethamphetamine (MDMA) in humans.

RATIONALE: Although 3,4-methylenedioxymethamphetamine (MDMA; Ecstasy) has been reported to cause fatal hyperthermia, few studies of the effects of MDMA on core body temperature in humans have been conducted demonstrating increased body temperature. In rats, MDMA causes hyperthermia at warm ambient temperatures but hypothermia at cold ones. OBJECTIVES: In this study, the physiological and subjective effects of MDMA in humans were determined at cold (18 degrees C) and warm (30 degrees C) ambient temperatures in a temperature and humidity-controlled laboratory. METHODS: Ten healthy volunteers who were recreational users of MDMA were recruited. Four laboratory sessions were conducted in a 2x2 design [i.e., two sessions at 30 degrees C and two at 18 degrees C, two during MDMA (2 mg/kg, p.o.) and two during placebo, in double-blind fashion]. Core body temperature (ingested radiotelemetry pill), skin temperature (four weighted sites), heart rate, blood pressure, metabolic rate (indirect calorimetry), shivering (electromyogram levels), and sweat rate (capacitance hygrometry) were measured as well as subjective effects for several time periods following capsule ingestion. RESULTS: MDMA produced significant elevations in core body temperature and metabolic rate in both warm and cold conditions. MDMA also produced significant elevations in blood pressure and heart rate and significantly increased several ratings of subjective effects similar to those previously reported. There were no differences related to ambient temperature for any of the subjective effects, except that ratings of cold and warm were appropriate to the ambient temperature and were not influenced by MDMA. CONCLUSIONS: Unlike findings in rats, MDMA increased core body temperature regardless of ambient temperature in humans. These increases appeared related to increases in metabolic rate, which were substantial. These findings warrant further investigations on the role of MDMA and other stimulants in altering metabolism and thermogenesis.

Adolescent↗
PubMed2005

Pathophysiology and treatment of menopausal hot flashes.

Hot flashes are the most common symptom of menopause. Although the appearance of hot flashes coincides with estrogen withdrawal, this does not entirely explain the phenomenon because estrogen levels do not differ between symptomatic and asymptomatic women. Luteinizing throughout? hormone pulses do not produce hot flashes nor do changes in endogenous opiates. Recent studies suggest that hot flashes are triggered by small elevations in core body temperature (T(c)) acting within a reduced thermoneutral zone in symptomatic postmenopausal women. This narrowing may be due to elevated central noradrenergic activation, a contention supported by observations that clonidine and some relaxation procedures ameliorate hot flashes. Because hot flashes are triggered by T(c) elevations, procedures to reduce T(c), such as lowering ambient temperature, are beneficial. Estrogen ameliorates hot flashes by increasing the T(c) sweating threshold, although the underlying mechanism is not known. Recent studies of hot flashes during sleep call into question their role in producing sleep disturbance.

Adrenergic alpha-Agonists↗
PubMed2005

Effects of symptomatic status and the menstrual cycle on hot flash-related thermoregulatory parameters.

OBJECTIVE: To compare core body temperature variation, sweating thresholds, and sweat rate in symptomatic and asymptomatic postmenopausal women and in eumenorrheic women in the follicular and luteal phases. DESIGN: Twelve symptomatic and 10 asymptomatic postmenopausal women and 12 eumenorrheic women were recorded in a temperature- and humidity-controlled laboratory during thermoneutral and warm conditions. Core body temperature variation was measured with an ingested radiotelemetry pill, basal body temperature with a rectal thermistor, skin temperature with four skin surface thermistors, and sweat rate with a capacitance hygrometer. RESULTS: Symptomatic women had significantly lower sweating thresholds and higher maximum sweat rates compared with all other women. These results could not be explained by differences in estrogen, progesterone, or body mass index. CONCLUSIONS: Postmenopausal women with hot flashes are uniquely characterized by low sweating thresholds and high sweat rates, relative to asymptomatic and eumenorrheic women.

Adult↗
PubMed2004

Increased tyrosine phosphorylation mediates the cooling-induced contraction and increased vascular reactivity of Raynaud's disease.

OBJECTIVE: Increased levels of protein tyrosine kinase (PTK) are mechanistically associated with increased contractile responsiveness to cooling. This study tests the hypothesis that increased PTK activity mediates the increased vascular reactivity to agonists and cooling associated with primary Raynaud's disease (RD). METHODS: The response of dermal arterioles isolated from control (n = 29) and RD (n = 29) subjects to contractile and dilatory agents at 37 degrees C and 31 degrees C was characterized using the microvessel perfusion technique. Fluorescence immunohistochemistry was used to measure tyrosine phosphorylation. RESULTS: At 37 degrees C, arteries from RD patients exhibited similar sensitivity to the specific alpha(2)-adrenergic agonist UK 14,304, to serotonin, and to angiotensin II. At 31 degrees C, however, the response to all 3 agonists was greater in the arterioles from the RD patients than in those from the control subjects. Agonist-induced contraction at both temperatures was reversed by cumulative addition of the PTK inhibitors genistein (1-30 microM) and tyrphostin 47 (0.1-10 microM). All arterioles from control subjects relaxed slightly in response to cooling, whereas more than half of those from RD patients contracted. This cooling-induced contraction was reversed by the cumulative addition of genistein. The 3 agonists elicited large increases in tyrosine phosphorylation only in arterial segments from RD patients at 31 degrees C. Cooling from 37 degrees C to 31 degrees C elicited a large increase in tyrosine phosphorylation in arterioles from RD patients, but not those from control subjects. All increases in tyrosine phosphorylation could be prevented by genistein. CONCLUSION: Increased tyrosine phosphorylation mediates cooling-induced contraction and the increased vascular reactivity of skin arterioles from individuals with RD.

Adrenergic alpha-Agonists↗
PubMed2004

Lack of sleep disturbance from menopausal hot flashes.

OBJECTIVE: To determine whether hot flashes produce disordered sleep in symptomatic postmenopausal women. DESIGN: Controlled laboratory study. SETTING: Healthy volunteers in a university medical center. PATIENT(S): Symptomatic and asymptomatic postmenopausal women and premenopausal women, all of similar ages (46-51 years). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Sleep electroencephalogram recordings, sternal skin conductance to record hot flashes, multiple sleep latency test to assess sleepiness, simple and divided attention performance tests, sleep and fatigue questionnaires. RESULT(S): Nineteen women were not selected for the following reasons: seven failed the drug screen, two had sleep apnea and periodic limb movements, one had periodic limb movements alone, two had body mass index (BMI) >30, one had hypertension, and six asymptomatic women had hot flashes in the laboratory. There were no significant group differences on any sleep stage measure. For example, for cycling vs. symptomatic vs. asymptomatic women: total sleep time, 6.9 +/- 0.7, 7.0 +/- 0.4, 7.0 +/- 0.4 hours; percentage stage 1 (light) sleep, 9.3% +/- 4.2%, 10.4% +/- 2.5%, 10.5% +/- 3.9%; number of brief arousals, 89.6 +/- 30.1, 111.9 +/- 45.8, 99.4 +/- 22.2; number of awakenings, 4.8 +/- 3.3, 6.7 +/- 2.1, 6.9 +/- 3.5. An average of 5.2 +/- 2.9 (+/-SD, range 1-18) hot flashes/night occurred in the symptomatic women. Of arousals occurring within 2 minutes of a hot flash, 46.7% occurred before, 46.7% occurred after, and 5.6% occurred simultaneously. Of awakenings occurring within 2 minutes of a hot flash, 55.2% occurred before, 40.0% after, and 5% simultaneously. There were no significant group differences on the multiple sleep latency test or any performance test or questionnaire measure. CONCLUSION(S): These data provide no evidence that hot flashes produce sleep disturbance in symptomatic postmenopausal women. Previous reports of increased sleep disturbance at menopause may be due to disorders that were screened out, such as sleep apnea and drug use.

Arousal↗
PubMed2002

Estrogen raises the sweating threshold in postmenopausal women with hot flashes.

OBJECTIVE: To determine if estrogen ameliorates hot flashes by raising the core body temperature sweating threshold, by reducing core body temperature fluctuations, and/or by reducing sympathetic activation (as measured by plasma 3-methoxy-4-hydroxyphenylglycol). DESIGN: Laboratory physiological study. SETTING: University medical center. PATIENT(S): Twenty-four healthy postmenopausal women reporting frequent hot flashes. INTERVENTION(S): Participants were randomly assigned, in double-blind fashion, to receive 1 mg/d 17beta-estradiol orally or placebo for 90 days. MAIN OUTCOME MEASURE(S): Core body temperature, core body temperature fluctuations, mean skin temperature, sternal sweat rate, laboratory hot flash counts (sternal skin conductance), plasma 3-methoxy-4-hydroxyphenylglycol. RESULT(S): The E(2) group had significant increases in plasma E(2) (8 +/- 2 vs. 132 +/- 22 pg/mL) and core body temperature sweating threshold (37.98 +/- 0.09 vs. 38.14 +/- 0.09 degrees C) and decreases in plasma FSH (58.8 +/- 8.9 vs. 40.1 +/- 7.6 mIU/mL) and hot flashes (1.4 +/- 0.5 vs. 0.6 +/- 0.6). These changes did not occur in the placebo group. There were no significant changes in any other measure. CONCLUSION(S): E(2) ameliorates hot flashes by raising the core body temperature sweating threshold, but does not affect core temperature fluctuations or plasma 3-methoxy-4-hydroxyphenylglycol.

Body Temperature↗
PubMedDate not supplied

Measurement of hot flashes by sternal skin conductance and subjective hot flash report in Puebla, Mexico.

OBJECTIVE: To measure hot flashes by sternal skin conductance in an urban Mexican population and to determine variables associated with hot flash reporting and measurement. DESIGN: From June 1999 to August 2000, 67 perimenopausal women aged 40 to 65 years participated in interviews, anthropometric measures, and a 2-h recording of sternal skin conductance. Changes in sweating were used to demonstrate the presence/absence of a hot flash. During the test, women were asked to report if they experienced a hot flash. RESULTS: During the study period, 10 women reported and demonstrated every hot flash, 24 women never reported or demonstrated a hot flash, 7 demonstrated hot flashes but did not report any of them, 7 reported hot flashes but did not demonstrate any of them, and 19 showed a mixture of responses. Women who demonstrated hot flashes by sternal skin conductance were measured in a warmer room, had more years of education, consumed more eggs as a child, recalled a heavier weight at age 18, and had a lower body mass index at interview compared with women who did not demonstrate hot flashes by sternal skin conductance. Women who subjectively reported hot flashes were measured in a warmer room, were more likely to be postmenopausal, reported more frequent consumption of coffee, and spent fewer months breast-feeding their last child compared with women who did not report the experience of hot flashes during the testing period. CONCLUSION: Room temperature explained part of the variation between women who did and did not demonstrate hot flashes via sternal skin conductance, between women who did and did not report the experience of hot flashes, and between women who did and did not demonstrate concordance in objective and subjective measures. In addition to room temperature, coffee intake, months spent breast-feeding the last child, and recalled weight at age 18 were important variables predicting hot flash experience.

Adult↗
PubMedDate not supplied

Core body temperature variation in symptomatic and asymptomatic postmenopausal women: brief report.

OBJECTIVE: To determine if core body temperature (T) fluctuations occur in asymptomatic as well as symptomatic postmenopausal women. DESIGN: Tc was recorded with an ingested radiotelemetry pill in symptomatic postmenopausal women who had a hot flash in the laboratory, in symptomatic women who did not have a hot flash in the laboratory, and in asymptomatic postmenopausal women. RESULTS: There were no significant differences in mean Tc or Tc variation, as measured by the standard deviation, among the three groups. CONCLUSION: Tc fluctuations are not unique to symptomatic postmenopausal women.

Analysis of Variance↗
PubMedDate not supplied

Hot flashes, core body temperature, and metabolic parameters in breast cancer survivors.

OBJECTIVE: To examine core body temperature, energy expenditure, and respiratory quotient among breast cancer survivors experiencing hot flashes and compare these data to published studies from healthy women. DESIGN: In an observational study, nine breast cancer survivors with daily hot flashes who met specified criteria spent 24 hours in a temperature- and humidity-controlled whole-room indirect calorimeter (ie, metabolic room). Demographic and disease/treatment information were obtained and the following were measured: hot flashes via sternal skin conductance monitoring (sampled every second); core body temperature via an ingested radiotelemetry pill (sampled every 10 seconds); and energy expenditure and respiratory quotient via a whole-room indirect calorimeter (calculated every minute). RESULTS: Circadian analysis of core temperature indicated wide variability with disrupted circadian rhythm noted in all women. Core temperature began to rise 20 minutes pre-flash to 7 minutes pre-flash (0.09 degrees C increase). Increases in energy expenditure and respiratory quotient increased with each hot flash. CONCLUSIONS: Findings are comparable to published data from healthy women and warrant replication in larger, more diverse samples of women treated for breast cancer.

Aged↗
PubMedDate not supplied

Effects of REM sleep and ambient temperature on hot flash-induced sleep disturbance.

OBJECTIVE: To determine whether hot flashes produce sleep disturbance in postmenopausal women. DESIGN: This study was performed in a university medical center laboratory with 18 postmenopausal women with hot flashes, six with no hot flashes, and 12 cycling women, all healthy and medication free. Polysomnography, skin and rectal temperatures, and skin conductance to detect hot flashes were recorded for four nights. Nights 2, 3, and 4 were run at 30 degrees C, 23 degrees C, and 18 degrees C in randomized order. RESULTS: During the first half of the night, the women with hot flashes had significantly more arousals and awakenings than the other two groups and the 18 degrees C ambient temperature significantly reduced the number of hot flashes, from 2.2 +/- 0.4 to 1.5 +/- 0.4. These effects did not occur in the second half of the night. In the first half of the night, most hot flashes preceded arousals and awakenings. In the second half, this pattern was reversed. CONCLUSIONS: In the second half of the night, rapid eye movement sleep suppresses hot flashes and associated arousals and awakenings. This may explain previous discrepancies between self-reported and laboratory-reported data in postmenopausal women with hot flashes.

Cold Temperature↗