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PubMed1996

Differential distribution of CaM kinases and induction of c-fos expression by flashing and sustained light in rat retinal cells.

PURPOSE: To examine the expression of c-fos proto-oncogene and phosphorylation of cAMP responsive element binding (CREB) protein in the rat retina after changes in the light-dark condition. METHODS: Rats were exposed to both steady light and flashing light and were killed at the end of light exposure. The retinas were analyzed by in situ hybridization using single-stranded RNA probes for c-fos transcripts and by immunocytochemistry using phosphoSer-133 specific CREB antiserum, anti-calcium calmodulin dependent protein (CaM) kinase II, and anti-CaM kinase IV. RESULTS: c-fos mRNA was expressed in the outer half of the inner nuclear layer (INL) and in the ganglion cell layer (GCL) after 30 minutes of sustained light. After 30 minutes of flashing light, c-fos expression also was detected in the inner border of the INL. Phosphorylated CREB immunoreactive nuclei had similar distribution after steady and flashing light. Both CaM kinase II and CaM kinase IV, which phosphorylate CREB at Ser 133 in vitro, were expressed in the GCL and in the INL. CaM kinase II, however, was localized in the inner border of the INL, whereas CaM kinase IV was distributed in the outer half of the INL. CONCLUSIONS: These results suggest that the differential expression of c-fos mRNA induced by flashing and sustained light may reflect the CREB phosphorylation by CaM kinases in a different subpopulation of retinal cells.

Animals↗
PubMedDate not supplied

Functional evaluation of transplanted kidneys by Gd-DTPA enhanced turbo FLASH MR imaging.

We evaluated the usefulness of dynamic turbo FLASH MR imaging in the differential diagnosis of complications after renal transplantation in 17 patients (10 from living relatives and 7 from cadavers). Coronal turbo FLASH dynamic images were obtained every 5 sec for 5 min after an intravenous bolus injection of Gd-DTPA. Corticomedullary differentiation (CMD) on spin echo coronal T1-weighted images and MR renogram patterns of the renal cortex and medulla were obtained for quantitative analysis of the Gd-DTPA-enhanced dynamic turbo-FLASH images. The signal intensity ratio of the medulla to cortex after Gd-DTPA enhancement was compared among four groups: normal (n = 9), acute tubular necrosis (ATN) or cyclosporine A (CyA) tubulopathy (n = 6), acute rejection (AR) in the living related donor kidney (n = 4), and AR in the cadaveric kidney (n = 5). Although loss of CMD was seen in severe renal dysfunction in the transplanted kidneys, there was considerable overlap among the four groups. On dynamic study, there was significant differences in the signal intensity ratio of the medulla to cortex between normally functioning kidneys or ATN/CyA tubulopathy and AR (p < 0.01). In patients with severe renal dysfunction, the arterial cortical peak was indistinct. In conclusion, MR renograms obtained from dynamic turbo FLASH MR imaging played a significant role in evaluating dysfunction of the renal transplant.

Acute Disease↗
PubMed2005

A behavioral group treatment program for menopausal hot flashes: results of a pilot study.

In the present study, we tested the effectiveness of a cognitive-behavioral group treatment (CBGT) for hot flashes in menopausal women. Treatment was administered over 8, 90 min weekly sessions and consisted of education, relaxation training and cognitive restructuring. Nineteen women meeting STRAW staging criteria for the menopause transition (stages -1 to +1) were randomly assigned to immediate or delayed treatment (wait list) and were asked to monitor their hot flashes and night sweats prospectively. They also completed questionnaires, including the Women's Health Questionnaire and the Menopause Specific Quality of Life Questionnaire to determine psychosocial benefits of treatment. Results suggested that the CBGT was moderately successful in reducing the frequency of total vasomotor symptoms [F (1, 17) = 6.16, p < .01], as measured by daily symptom diaries. While there were arithmetic improvements in psychosocial functioning in this sample, these results were not significant. Despite the limitations of small sample size and possible placebo effect, this pilot study supports the notion that cognitive-behavioral interventions aimed at reducing vasomotor symptoms may be of value for menopausal hot flashes when administered in a small-group format.

Cognitive Behavioral Therapy↗
PubMed2004

Management of hot flashes in breast cancer survivors and men with prostate cancer.

Hot flashes are a significant complaint among many breast cancer survivors and many men undergoing androgen deprivation therapy for prostate cancer. Several therapeutic approaches are available to the suffering man or woman. Many of these individuals have tried nonpharmacologic and nonconventional approaches. However, most nonpharmacologic treatments have not been compared with placebo or were not more effective than placebo in prospective, randomized clinical trials. The most effective nonhormonal treatments for hot flashes include agents from the selective serotonin or noradrenergic reuptake inhibitor (SSRI/SNRI) family. Paroxetine, 10 mg/d, or venlafaxine, 37.5 mg/d, are reasonable initial dosages, and if symptoms do not improve within a week or two, the dosage can be doubled. Gabapentin appears to provide similar benefits, but direct comparisons have not been reported. Because of the strong association between gonadal hormones and breast and prostate cancer, the use of hormonal agents to treat hot flashes in these patients has been limited. However, such hormonal therapies as depomedroxyprogesterone acetate can be prescribed for an informed individual who experiences bothersome symptoms despite nonhormonal treatments.

Amines↗
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↗
PubMed2004

Hot flashes refractory to HRT and SSRI therapy but responsive to gabapentin therapy.

There is a need for alternative therapies for hot flashes, as hormone replacement therapy (HRT) is associated with increased rates of breast cancer and heart disease, and some women fail to respond to HRT. A 32-year-old woman with surgically-induced menopause experienced 20-30 severe hot flashes per day and failed to respond to various formulations of HRT and selective serotonin reuptake inhibitor (SSRI) therapy for 17 years. She markedly responded to gabapentin therapy. Gabapentin, SSRIs, and estrogen may act at different cellular targets in the treatment of hot flashes.

Acetates↗
PubMed2005

Hot flashes are associated with psychological symptoms of anxiety and depression in peri- and post- but not premenopausal women.

OBJECTIVE: To explore the relationship between anxiety, depression, vasomotor symptoms, and menopausal status among middle-aged women. DESIGN: A population-based study involving a rural Taiwanese population. Participants received a structured questionnaire, which included the hospital anxiety and depression scale (HADS), gynecological history and a checklist of menopausal symptoms in the most recent 2 weeks. RESULTS: A total of 1273 women with no history of surgical menopause and hormonal therapy history participated. The mean anxiety, depression, and total HADS scores were 4.3 +/- 3.3, 3.3 +/- 2.8 and 7.6 +/- 5.3, respectively, and did not differ according to menopausal status. A total of 10.5% participants reported hot flashes within the previous 2 weeks. After controlling for educational status and insomnia, anxiety (6.0 +/- 3.8 versus 4.1 +/- 3.1) and depression scores (4.0 +/- 3.3 versus 3.2 +/- 2.7) were significantly higher (p < 0.001) compared with those without hot flashes. These differences were attributed to peri- and postmenopausal subjects. CONCLUSIONS: Hot flashes in peri- and postmenopausal women were associated with anxious and depressive symptoms in East Asian population with low prevalence of vasomotor symptoms.

Adult↗
PubMed2004

Pilot study using gabapentin for tamoxifen-induced hot flashes in women with breast cancer.

In this pilot study, 22 women with breast cancer on tamoxifen therapy with at least two hot flashes a day took oral gabapentin at 300 mg three times a day for 4 weeks. The 16 women who completed the study had a mean decrease in hot flash duration of 73.6% (P = 0.027), frequency of 44.2% (P < 0.001), and severity of 52.6% (P < 0.001), with a complete response in 8/16 women. Side effects reported by four women who did not complete 4 weeks of the study were nausea (1/4), rash (1/4) and excessive sleepiness (3/4). Two additional patients did not provide complete data. Gabapentin is a promising new agent in the treatment of tamoxifen induced hot flashes, and should be studied further.

Acetates↗
PubMed1999

Progressive prostate cancer associated with use of megestrol acetate administered for control of hot flashes.

Low doses of megestrol acetate are frequently used for treatment of hot flashes in men having androgen ablation for prostate cancer. We report a case in which megestrol acetate (20 mg bid) was administered for symptomatic control of hot flashes in a medically castrated patient with prostate cancer. The patient was subsequently noted to have a rising prostate-specific antigen (PSA) level. Megestrol acetate administration was discontinued, and the PSA level declined. These data indicate that even the low doses of megestrol acetate used for control of hot flashes can be associated with PSA increases in some patients with prostate cancer.

Aged↗
PubMed2005

State of the science: hot flashes and cancer. Part 2: management and future directions.

PURPOSE/OBJECTIVES: To critically evaluate and synthesize intervention research related to hot flashes in the context of cancer and to identify implications and future directions for policy, research, and practice. DATA SOURCES: Published, peer-reviewed articles and textbooks; editorials; and computerized databases. DATA SYNTHESIS: Although a variety of pharmacologic and nonpharmacologic treatments are available, they may not be appropriate or effective for all individuals. CONCLUSIONS: The large and diverse evidence base and current national attention on hot flash treatment highlight the importance of the symptom to healthcare professionals, including oncology nurses. IMPLICATIONS FOR NURSING: Using existing research to understand, assess, and manage hot flashes in the context of cancer can prevent patient discomfort and improve the delivery of evidence-based care.

Antidepressive Agents↗
PubMed2006

Adjuvant chemotherapy followed by goserelin compared with either modality alone: the impact on amenorrhea, hot flashes, and quality of life in premenopausal patients--the International Breast Cancer Study Group Trial VIII.

PURPOSE: The purpose of this article is to compare quality of life (QOL) and menopausal symptoms among premenopausal patients with lymph node-negative breast cancer receiving chemotherapy, goserelin, or their sequential combination, and to investigate differential effects by age. PATIENTS AND METHODS: We evaluated QOL data from 874 pre- and perimenopausal women with lymph node-negative breast cancer who were randomly assigned to receive six courses of classical cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy, ovarian suppression with goserelin for 24 months, or six courses of classical CMF followed by 18 months of goserelin. We report QOL data collected during 3 years after random assignment in patients without disease recurrence. RESULTS: Overall, patients receiving goserelin alone showed a marked improvement or less deterioration in QOL measures over the first 6 months than those patients treated with CMF. There were no differences at 3 years after random assignment according to treatment except for hot flashes. As reflected in the hot flashes scores, patients in all three treatment groups experienced induced amenorrhea, but the onset of ovarian function suppression was slightly delayed for patients receiving chemotherapy. Younger patients (< 40 years) who received goserelin alone returned to their premenopausal status at 6 months after the cessation of therapy, while those who received CMF showed marginal changes from their baseline hot flashes scores. CONCLUSION: Age-adjusted risk profiles that consider patient-reported outcomes enable patients to adapt to their disease and treatment, such as considering the trade-offs between delayed endocrine symptoms, but higher risk of permanent menopause with chemotherapy, and immediate but reversible endocrine symptoms with goserelin, in younger premenopausal patients.

Adult↗
PubMed2004

Selective serotonin-reuptake inhibitors for the treatment of hot flashes.

OBJECTIVE: To review the literature evaluating the use of selective serotonin-reuptake inhibitors (SSRIs) for the treatment of hot flashes. DATA SOURCES: Biomedical literature was accessed through MEDLINE (1966-June 2003), MD Consult, and references of reviewed articles. Key search terms used were hot flashes, vasomotor symptoms, antidepressants, and SSRIs. DATA SYNTHESIS: Recent evidence from the Women's Health Initiative precludes the use of traditional hormonal therapy in some women. Nonhormonal therapies are possible options, but conflicting evidence of efficacy exists. CONCLUSIONS: Although further studies are warranted, preliminary data suggest that SSRIs are generally modestly successful in reducing the frequency and severity of hot flashes.

Clinical Trials as Topic↗
PubMed2003

Hot flashes--a review of the literature on alternative and complementary treatment approaches.

Hot flashes are a common experience for menopausal women, with an 85-percent incidence in the West. With the increased knowledge of side effects attributable to conventional treatment options, more women are exploring natural alternatives. Although more definitive research is necessary, several natural therapies show promise in treating hot flashes without the risks associated with conventional therapies. Soy and other phytoestrogens, black cohosh, evening primrose oil, vitamin E, the bioflavonoid hesperidin with vitamin C, ferulic acid, acupuncture treatment, and regular aerobic exercise have been shown effective in treating hot flashes in menopausal women.

Female↗
PubMed2005

The potential of 5-hydryoxytryptophan for hot flash reduction: a hypothesis.

Hormone replacement therapy (HRT) is contraindicated in women with a history of breast cancer or a high risk of breast cancer development. Recent results from large clinical trials, such as the Women's Health Initiative, have demonstrated increased risks of thromboembolic events and a moderate increased risk of breast cancer in women using conjugated estrogens and progestogens. There is a need for viable non-hormonal alternative treatments to HRT, such as nutritional and botanical therapies, in this population of women, who tend to experience more significant vasomotor symptoms. Safe and effective therapies that do not stimulate breast cell proliferation could prove extremely useful for the management of such symptoms for women in both low- and high-risk breast cancer populations. As a non-hormonal treatment, anti-depressants, such as selective serotonin reuptake inhibitors (SSRIs), have been shown to improve hot flash symptoms in women. The proposed mechanism is related to an increase in serotonin allowing for an increase in the set point of the brain's thermoregulator. In small clinical studies, the administration of tryptophan and 5-hydroxytryptophan (5HTP), the precursors of serotonin, have been shown to reduce depressive symptoms, possibly by enhancing the synthesis of serotonin. Thus, increased serotonin levels may have the ability to decrease hot flashes in a mechanism similar to that of SSRIs without the risks of breast cell stimulation. This would be particularly desirable for menopausal women with breast cancer or with risks of breast cancer. This article discusses the background information on hot flashes, SSRIs, tryptophan, and 5HTP, and possible clinical application of 5HTP for menopausal women with breast cancer risk.

5-Hydroxytryptophan↗
PubMed2005

Hot-flashes in breast cancer survivors: effectiveness of low-dosage fluoxetine. A pilot study.

Breast carcinoma survivors suffering from hot-flashes experience a negative impact on their quality of life. Antidepressants have recently been proven to be effective in these women, significantly reducing the vasomotor symptoms. With this in mind, a single-arm clinical trial low-dose regimen of Fluoxetine (10 mg/day for 4 weeks) was given to twenty symptomatic breast cancer patients. Among the 12 women evaluated at the end of treatment, a statistically significant reduction of the mean number of daily hot-flashes (-36.3%, p = 0.001) and hot-flashes score (-46.2%, p = 0.0006) had been detected as compared to the baseline data. Although the dosage of Fluoxetine used in these trials was lower than earlier published, it should be noted that these positive results were achieved without any relevant side effects.

Adult↗
PubMedDate not supplied

Pathophysiology and management of hot flashes.

Depending on their frequency and severity, hot flashes can be a major source of distress for individuals with cancer, particularly women with a history of breast cancer and men with prostate cancer. Characterized by increased skin temperature, skin conductance, and heart rate, hot flashes are associated with somatic, behavioral, and emotional manifestations. In this article, the authors review the prevailing theories on the pathophysiology of hot flashes and assess the major treatment interventions, such as hormonal agents, nonhormonal pharmacotherapy (including antidepressants), and complementary/alternative medicine options.

Antidepressive Agents↗
PubMed1999

Comparison of iron oxide particles (AMI 227) with a gadolinium complex (Gd-DOTA) in dynamic susceptibility contrast MR imagings (FLASH and EPI) for both phantom and rat brain at 1.5 Tesla.

The goal of the study was to compare, in phantom and normally perfused rat brain tissue, a superparamagnetic iron oxide particle-based contrast agent (AMI 227) with a low-molecular-weight gadolinium chelate, gadolinium tetraazacyclododecanetetraacetic acid (Gd-DOTA), in two susceptibility contrast magnetic resonance imaging (MRI) modes [fast low-angle shot sequence (FLASH) and echoplanar imaging (EPI)]. A phantom consisting of dilution series of both contrast agents was manufactured. Dilutions were obtained with isotonic serum from the available agent solutions (0.5 mmol Gd/mL Gd-DOTA; 350 mumol Fe/mL AMI 227). Eighteen rats were studied. Contrast agent (0.1 mL) was bolus injected in each rat, and dynamic MRI was performed (first pass of the contrast agent) in rat brain. The doses of AMI 227 injected were extrapolated from the phantom experiment: 0.2 mmol/kg body weight of Gd-DOTA and 7, 14, and 28 mumol Fe/kg body weight of AMI 227 were injected. For both sequences, signal-to-noise ratios (S/N) were measured on each tube of the phantom and on rat brain from each image of the dynamic imaging. S/N was plotted versus contrast dilution (phantom) and versus time (rats). In the FLASH sequence, a well-shaped curve (S/N decrease, S/N peak decrease, S/N increase) of the first pass of the contrast agent was demonstrated for Gd-DOTA and for AMI 227 (7 mumol Fe/kg body weight). In the EPI sequence, a well-shaped curve was demonstrated for Gd-DOTA, and a plateau effect was noted for both concentrations of AMI 227. With the FLASH technique, dynamic susceptibility contrast imaging of rat brain can be performed with very low concentrations of AMI 227 compared with the Gd-DOTA concentration (0.2 mmol Gd/kg body weight) used in clinical practice. This could be of interest in perfusion imaging, because it may allow for first-pass susceptibility imaging after administration of a small volume in a narrow bolus.

Animals↗
PubMed2000

A comparison between segmented k-space FLASH and interleaved spiral MR coronary angiography sequences.

A direct comparison of segmented fast low-angle short (FLASH) imaging and interleaved spiral magnetic resonance coronary angiography (MRCA) during free respiration using navigator echo has been performed. MRCA images were acquired in 30 normal subjects and 15 patients with coronary artery disease (CAD). Images of the right coronary artery were acquired during free respiration using navigator echo gating for both a segmented k-space FLASH sequence (8 views/segment, segment duration 105 msec) and an interleaved spiral sequence (20 interleaves, spiral read-out period 19 msec). Image quality was scored by three independent blinded observers, and coronary artery signal-to-noise ratio (SNR) and coronary artery/epicardial fat contrast-to-noise ratio (CNR) were measured. There was a significant improvement in image quality when coronary images were acquired with the interleaved spiral sequence (spiral 2. 3 vs. FLASH 1.8; P = 0.002). This was associated with an increase in the coronary artery SNR (16.6 +/- 6.9 vs. 11.8 +/- 5.0; P < 0.001), the coronary artery/epicardial fat CNR (12.5 +/- 6.1 vs. 7.4 +/- 4.0, P < 0.001), and the image resolution (256 x 256 vs. 256 x 128). However, there was a 12% increase in acquisition time for the interleaved spiral sequence. Image quality, SNR, CNR, and resolution can be improved using an interleaved spiral sequence. These improvements are secondary to the intrinsic characteristics of spiral imaging and the short acquisition period, which reduces the effects of both cardiac and respiratory motion.

Adult↗