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[Effects of flashing light on ocular growth and development of myopia in pigmented guinea pigs].

OBJECTIVE: To investigate the effects of flashing light exposure on ocular growth and development of myopia in guinea pigs. METHODS: Thirty 4-week-old pigmented guinea pigs were randomly divided into three groups. Animals in group I were reared with the flashing light continuously and lasted for 6 weeks. The flashing frequency was 15 times per minutes and every flash includes 2 seconds light on and 2 seconds dark. Animals in group II and III were reared with normal light on, and the illumination cycle was 12 hours light/12 hours dark in group II and 24 hours light in group III. After 6 weeks, the effects of flashing light on eye development were assessed by cycloplegic retinoscopy, a-scan ultrasonography and eye weight. The histopathology changes of sclera, choroids and retina in posterior pore of the eye were examined using light microscope and transmission electron microscope. RESULTS: At the end of the treatment period, guinea pigs reared in flashing light exhibited -7.00 D myopia, eye axial elongated 0.56 microm, and the weight increased 68 mg. The histopathology examination showed that the posterior sclera fibroblast become more active, the cell number increased, and the place between fibers became larger, the posterior choroids became thinned, and the outer membrane of photoreceptor cells became shorter and irregular, when compared with the control groups. CONCLUSION: Flashing light can promote ocular growth and induce myopia in pigmented guinea pigs.

Animals↗

Mortality from flash floods: a review of national weather service reports, 1969-81.

Of all weather-related disasters that occur in the United States, floods are the main cause of death, and most flood-related deaths are attributed to flash floods. Whenever a weather-related disaster involves 30 or more deaths or more than $100 million in property damage, the National Weather Service (NWS) forms a survey team to investigate the disaster and write a report of findings. All NWS survey reports on flash floods issued during 1969-81 were reviewed to determine the mortality resulting from such floods, the effect of warnings on mortality, and the circumstances contributing to death. A total of 1,185 deaths were associated with 32 flash floods, an average of 37 deaths per flash flood. The highest average number of deaths per event was associated with the four flash floods in which dams broke after heavy rains. Although there were 18 flash floods in 1977-81 and only 14 in 1969-76, the number of deaths was 2 1/2 times greater during the earlier period. More than twice as many deaths were associated with flash floods for which the survey team considered the warnings inadequate than with those with warnings considered adequate. Ninety-three percent of the deaths were due to drowning and 42 percent of these drownings were car related. The other drownings occurred in homes, at campsites, or when persons were crossing bridges and streams. The need for monitoring dams during periods of heavy rainfall is highlighted.

Disasters↗

Effect of clonidine on hot flashes in postmenopausal women.

The effectiveness of clonidine in suppressing the occurrence of postmenopausal hot flashes was examined using a dose-response study design and objective recordings of hot flashes. Patients with frequent flashes were studied before and after oral administration of placebo and 0.1, 0.2, and 0.4 mg of clonidine daily for 2 weeks at each dose level. Finger temperature and skin resistance were recorded as indices of hot flash episodes. Four of 10 subjects beginning the study withdrew because of drug-related side effects. Clonidine was found to reduce significantly the frequency of hot flashes as compared with baseline (P less than .005) and with effects of the placebo (P less than .05). At the maximum dosage the mean rate of hot flash occurrence decreased 46%. It was concluded that clonidine does reduce the frequency of postmenopausal flashes.

Body Temperature↗

Nonhormonal therapies for menopausal hot flashes: systematic review and meta-analysis.

CONTEXT: Concern regarding the adverse effects of estrogen and other hormones for treating menopausal symptoms has led to demand for other options; however, the efficacy and adverse effects of nonhormonal therapies are unclear. OBJECTIVE: To assess the efficacy and adverse effects of nonhormonal therapies for menopausal hot flashes by reviewing published randomized controlled trials. DATA SOURCES: MEDLINE (1966-October 2005), PsycINFO (1974-October 2005), and the Cochrane Controlled Clinical Trials Register Database (1966-October 2005) were searched for relevant trials that provided data on treatment of menopausal hot flashes using 1 or more nonhormonal therapies. STUDY SELECTION: All English-language, published, randomized, double-blind, placebo-controlled trials of oral nonhormonal therapies for treating hot flashes in menopausal women measuring and reporting hot flash frequency or severity outcomes. DATA EXTRACTION: Trials were identified, subjected to inclusion and exclusion criteria, and reviewed. Data on participants, interventions, and outcomes were extracted and trials were rated for quality based on established criteria. A meta-analysis was conducted for therapies with sufficient trials reporting hot flash frequency outcomes. DATA SYNTHESIS: From 4249 abstracts, 43 trials met inclusion criteria, including 10 trials of antidepressants, 10 trials of clonidine, 6 trials of other prescribed medications, and 17 trials of isoflavone extracts. The number of daily hot flashes decreased compared with placebo in meta-analyses of 7 comparisons of selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) (mean difference, -1.13; 95% confidence interval [CI], -1.70 to -0.57), 4 trials of clonidine (-0.95; 95% CI, -1.44 to -0.47), and 2 trials of gabapentin (-2.05; 95% CI, -2.80 to -1.30). Frequency was not reduced in meta-analysis of trials of red clover isoflavone extracts and results were mixed for soy isoflavone extracts. Evidence of the efficacy of other therapies is limited due to the small number of trials and their deficiencies. Trials do not compare different therapies head-to-head and relative efficacy cannot be determined. CONCLUSION: The SSRIs or SNRIs, clonidine, and gabapentin trials provide evidence for efficacy; however, effects are less than for estrogen, few trials have been published and most have methodological deficiencies, generalizability is limited, and adverse effects and cost may restrict use for many women. These therapies may be most useful for highly symptomatic women who cannot take estrogen but are not optimal choices for most women.

Adrenergic alpha-Agonists↗

Physiology of hot flashes.

Hot flashes are the most common symptom of the climacteric, although prevalence estimates are lower in some rural and non-Western areas. The symptoms are characteristic of a heat-dissipation response and consist of sweating on the face, neck, and chest, as well as peripheral vasodilation. Although hot flashes clearly accompany the estrogen withdrawal at menopause, estrogen alone is not responsible since levels do not differ between symptomatic and asymptomatic women. Until recently it was thought that hot flashes were triggered by a sudden, downward resetting of the hypothalamic setpoint, since there was no evidence of increased core body temperature. Evidence obtained using a rapidly responding ingested telemetry pill indicates that the thermoneutral zone, within which sweating, peripheral vasodilation, and shivering do not occur, is virtually nonexistent in symptomatic women but normal (about 0.4 degrees C) in asymptomatic women. The results suggest that small temperature elevations preceding hot flashes acting within a reduced thermoneutral zone constitute the triggering mechanism. Central sympathetic activation is also elevated in symptomatic women which, in animal studies, reduces the thermoneutral zone. Clonidine reduces central sympathetic activation, widens the thermoneutral zone, and ameliorates hot flashes. Estrogen virtually eliminates hot flashes but its mechanism of action is not known.

Body Temperature Regulation↗

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↗

Hot flashes in breast cancer survivors.

Hot flashes can be a major problem for patients with a history of breast cancer. The precipitation of menopause in premenopausal women who undergo chemotherapy for breast cancer can lead to the rapid onset of hot flash symptoms that are more frequent and more severe than those associated with natural menopause. In addition, tamoxifen, historically the most commonly prescribed pharmacologic agent for the treatment of breast cancer, is associated with hot flashes in more than 50% of its users. Although estrogen relieves hot flashes in 80-90% of women who initiate treatment, its use in women with a history of breast cancer is controversial, and most physicians in the community will not use this treatment modality. In addition, the results of the long-awaited Women's Health Initiative study and other recent studies suggest that long-term estrogen therapy should not be recommended for most women for a variety of reasons. However, hot flashes in breast cancer survivors should no longer be considered untreatable, as there are many pharmacologic and nonpharmacologic treatments that can help alleviate this problem. This article reviews the current strategies for the management of hot flashes in breast cancer survivors and the evidence supporting their use.

Antidepressive Agents↗

Can hypnosis reduce hot flashes in breast cancer survivors? A literature review.

Hot flashes are a significant problem for many breast cancer survivors and can cause discomfort, insomnia, anxiety, and decreased quality of life. In the past, the standard treatment for hot flashes has been hormone replacement therapy. However, recent research has found an increased risk of breast cancer in women receiving hormone replacement therapy. As a result, many menopausal women and breast cancer survivors reject hormone replacement therapy and many women want non-pharmacological treatment. In this critical review we assess the potential use of hypnosis in reducing the frequency and intensity of hot flashes. We conclude that hypnosis is a mind-body intervention that may be of significant benefit in treatment of hot flashes and other benefits may include reduced anxiety and improved sleep. Further, hypnosis may be a preferred treatment because of the few side-effects and the preference of many women for a non-hormonal therapy. Two case studies are included to illustrate hypnosis for hot flashes. However this intervention has not been adequately studied. We discuss an NIH-funded randomized clinical trial of hypnosis for hot flashes in breast cancer survivors that is presently being conducted.

Breast Neoplasms↗

Current alcohol use is associated with a reduced risk of hot flashes in midlife women.

AIMS: To examine the relation between current alcohol use, estradiol, estrone, and testosterone levels, and hot flashes in midlife women using a case-control study design. METHODS: Cases were midlife women (45-54 years) who reported ever experiencing hot flashes. Controls were midlife women (45-54 years) who reported never experiencing hot flashes. Each participant completed a questionnaire and provided a blood sample that was used to measure estradiol, estrone, and testosterone levels by enzyme-linked immunosorbent assay. RESULTS: The results indicate that current alcohol use (at least one day per month) was significantly associated with a reduced risk of hot flashes compared to non-use of alcohol, independent of age and smoking habits. The hot flashes experienced by current alcohol users were less severe and less frequent than those experienced by non-users of alcohol. Further, current alcohol users had similar levels of estradiol, estrone, and testosterone compared to non-users of alcohol. CONCLUSIONS: These data suggest that current alcohol use is associated with a reduced risk of any, severe, and frequent hot flashes in midlife women by a mechanism that may not include changes in sex steroid hormone levels.

Alcohol Drinking↗

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↗

FLASH-TB: an Application of Next-Generation CRISPR to Detect Drug Resistant Tuberculosis from Direct Sputum.

Offering patients with tuberculosis (TB) an optimal and timely treatment regimen depends on the rapid detection of Mycobacterium tuberculosis (Mtb) drug resistance from clinical samples. Finding Low Abundance Sequences by Hybridization (FLASH) is a technique that harnesses the efficiency, specificity, and flexibility of the Cas9 enzyme to enrich targeted sequences. Here, we used FLASH to amplify 52 candidate genes probably associated with resistance to first- and second-line drugs in the Mtb reference strain (H37Rv), then detect drug resistance mutations in cultured Mtb isolates, and in sputum samples. 92% of H37Rv reads mapped to Mtb targets, with 97.8% of target regions covered at a depth ≥ 10X. Among cultured isolates, FLASH-TB detected the same 17 drug resistance mutations as whole genome sequencing (WGS) did, but with much greater depth. Among the 16 sputum samples, FLASH-TB increased recovery of Mtb DNA compared with WGS (from 1.4% [IQR 0.5-7.5] to 33% [IQR 4.6-66.3]) and average depth reads of targets (from 6.3 [IQR 3.8-10.5] to 1991 [IQR 254.4-3623.7]). FLASH-TB identified Mtb complex in all 16 samples based on IS1081 and IS6110 copies. Drug resistance predictions for 15/16 (93.7%) clinical samples were highly concordant with phenotypic DST for isoniazid, rifampicin, amikacin, and kanamycin [15/15 (100%)], ethambutol [12/15 (80%)] and moxifloxacin [14/15 (93.3%)]. These results highlighted the potential of FLASH-TB for detecting Mtb drug resistance from sputum samples.

Humans↗

Comparing the effects of estrogen and an herbal medicine on peripheral blood flow in post-menopausal women with hot flashes: hormone replacement therapy and gui-zhi-fu-ling-wan, a Kampo medicine.

We investigated the association between blood flow in the extremities and hot flashes, and compared change in blood flow following hormone replacement therapy (HRT) and Gui-zhi-fu-ling-wan (Keishi-bukuryo-gan), a herbal therapy in post-menopausal women with hot flashes. Three hundred and fifty-two post-menopausal women aged 46-58 years (mean: 53.4 +/- 3.6 years) with climacteric complaints participated in the study. One hundred and thirty-one patients with hot flashes were treated with HRT (64 cases) or herbal therapy (67 cases). Blood flow was measured with laser doppler fluxmetry under the jaw, in the middle finger and in the third toe. Post-menopausal women with hot flashes (129 cases) showed significantly higher blood flow under the jaw (13.6 +/- 4.13) than women without hot flashes (166 cases) (5.48 +/- 0.84) (p < 0.0001). Blood flow at this site decreased significantly with either therapy (p < 0.0001). On the other hand, the administration of Gui-zhi-fu-lingwan significantly increased (p = 0.002) the blood flow in the lower extremities, whereas HRT decreased the blood flow. Thus, we have demonstrated that Gui-zhi-fu-ling-wan did not affect the activity of vasodilator neuropeptides on sensory neurons of systemic peripheral vessels uniformly. Therefore, Gui-zhi-fu-ling-wan, rather than HRT, is suggested as an appropriate therapy for treatment of hot flashes in the face and upper body with concomitant coldness in the lower body, which is one of the symptoms of menopause.

Administration, Oral↗

Pilot evaluation of venlafaxine hydrochloride for the therapy of hot flashes in cancer survivors.

PURPOSE: Hot flashes can be a prominent clinical problem for breast cancer survivors and men who undergo androgen-deprivation therapy. Anecdotal information suggested a low dose of a relatively new antidepressant, venlafaxine, could abrogate this clinical problem. MATERIALS AND METHODS: This study included 28 consecutive assessable patients entered onto a phase II clinical trial. Hot flash data were collected by daily diary questionnaires during a 1-week baseline period and then for 4 weeks, during which time patients received venlafaxine 12.5 mg orally twice daily. RESULTS: Fifty-eight percent of patients who completed the study had a greater than 50% reduction in hot flash scores (frequency times severity) during the fourth treatment week as compared with the baseline week. Median weekly hot flash scores were reduced by 55% from baseline during the fourth week of venlafaxine therapy. Therapy was generally well tolerated and appeared to alleviate fatigue, sweating, and trouble sleeping. CONCLUSION: Venlafoxine appears to represent an efficacious new method to alleviate hot flashes. Further evaluation of this compound for alleviating hot flashes is indicated.

Adult↗

Evaluation of soy phytoestrogens for the treatment of hot flashes in breast cancer survivors: A North Central Cancer Treatment Group Trial.

PURPOSE: Hot flashes represent a significant clinical problem for some breast cancer survivors. Safe, effective treatment is needed for this prominent clinical problem. Although it has been shown that estrogen or progesterone replacement therapy can alleviate this problem, there are continued safety concerns regarding the use of hormonal therapies in these women. Based on anecdotal information, we hypothesized that soy-derived phytoestrogens, weak estrogen-like substances in the soybean that demonstrate estrogen agonist and/or antagonist effects when they bind to estrogen receptors, could alleviate hot flashes. This current trial was designed to investigate this hypothesis. PATIENTS AND METHODS: This double-blind clinical trial involved breast cancer survivors with substantial hot flashes. After randomization, patients underwent a 1-week baseline period with no therapy. This was followed by 4 weeks of either soy tablets or placebo. The patients then crossed over to the opposite arm in a double-blind manner for the last 4 weeks. Patients completed a daily questionnaire documenting hot flash frequency, intensity, and perceived side effects. RESULTS: Of the 177 women who were randomized and started the study substance, 155 (88%) provided useable data over the first 5 weeks; 149 provided usable data over the entire 9 weeks. There was no suggestion that the soy product was more effective in reducing hot flashes than the placebo. At study completion, patients preferred the soy product 33% of the time, the placebo 37% of the time, and neither substance 31% of the time. No toxicity was observed. CONCLUSION: The soy product did not alleviate hot flashes in breast cancer survivors.

Adolescent↗

Gabapentin for hot flashes in prostate cancer.

OBJECTIVE: To report a case of successful treatment of refractory hot flashes with gabapentin in a patient with prostate cancer who was receiving combination antiandrogen and gonadotropin hormone-releasing hormone (GnRH) analog therapy. CASE SUMMARY: A 70-year-old white man with a history of advancing prostate cancer experienced disabling hot flashes from combination therapy with the antiandrogen bicalutamide and the GnRH analog goserelin acetate. He failed to respond to clonidine 0.1 mg twice daily, megestrol acetate 40 mg/d, diethylstilbestrol 1 mg/d, and venlafaxine 25 mg twice daily. The patient was then treated with gabapentin 600 mg once daily, at which time he experienced near-complete resolution of his symptoms. DISCUSSION: This case supports a previous report of the marked improvement in severity and duration of hot flashes associated with antiandrogen or GnRH analog therapy in prostate cancer. The mechanism by which gabapentin reduces hot flashes is unknown. CONCLUSIONS: Hot flashes resulting from antiandrogen or GnRH analog therapy are often difficult to treat and leave many patients disabled. Gabapentin has been shown to markedly reduce the severity, frequency, and duration of these hot flashes. Controlled trials are necessary to evaluate gabapentin against other therapeutic modalities.

Acetates↗

Pilot evaluation of paroxetine for treating hot flashes in men.

OBJECTIVE: To provide prospective information on the potential utility of paroxetine for treating hot flashes In men receiving androgen ablation therapy for prostate cancer. PATIENTS AND METHODS: Men with symptomatic androgen ablation therapy-related hot flashes were entered into this clinical trial between August 2001 and October 2003. After a baseline week of documentation of the frequency of hot flashes, patients were assigned to receive paroxetine; the initial dosage was 12.5 mg/d, and it was increased to 37.5 mg/d over the ensuing 4 weeks. RESULTS: Of the 24 patients in whom medication was initiated, 18 completed the 5-week study. In these patients, the median frequency of hot flashes decreased from 6.2 per day during the baseline week to 2.5 per day during the last study week. Hot flash scores (frequency x mean severity) during the same period decreased from 10.6 per day to 3.0 per day. Overall, paroxetine was well tolerated by most patients. CONCLUSION: The results from this trial suggest that paroxetine Is an effective agent for diminishing hot flashes in men receiving androgen ablation therapy.

Aged↗

New therapeutic approaches for hot flashes in women.

While most women will suffer from hot flashes at some point over their lifetime, most symptoms resolve with time. However, some women may experience severe and/or long-lasting hot flashes. Estrogen, the most effective treatment for hot flashes, is not generally recommended for women with a history of breast cancer or women at high risk of developing breast cancer. Moreover, long-term administration of estrogen to healthy women is associated with increased risks of cardiovascular disease, stroke, and breast cancer. Newer antidepressants from the selective serotonin or noradrenergic reuptake inhibitor family, such as venlafaxine and paroxetine, appear to be among the most effective nonhormonal agents for the treatment of hot flashes. New information demonstrates that gabapentin also is an effective nonhormonal therapy for hot flashes. In this review, we will discuss current knowledge of the epidemiology and pathophysiology of hot flashes, along with treatment options. We will focus on nonhormonal treatments that have been studied in prospective randomized clinical trials, and will present an algorithm for the treatment of symptomatic patients.

Aged↗

Long term use of megestrol acetate by cancer survivors for the treatment of hot flashes.

BACKGROUND: Hot flashes are often a troublesome symptom in breast carcinoma survivors and men with prostate carcinoma who have undergone androgen deprivation therapy. A previous clinical study demonstrated that, on a short term basis, low dose megestrol acetate markedly reduced hot flashes and was well tolerated. Little information has been available regarding the long term use of low dose megestrol acetate for hot flashes. METHODS: Patients previously enrolled on a randomized placebo-controlled trial that evaluated the short term use of megestrol acetate for hot flashes were contacted and interviewed by telephone. RESULTS: A total of 132 persons were contacted. Nine percent of the patients discontinued megestrol acetate after resolution of their hot flashes. Forty-five percent of the patients contacted were continuing to utilize megestrol acetate approximately 3 years beyond the conclusion of the 1992 study. Three-quarters of these patients were utilizing < or =20 mg of megestrol acetate per day. Potential toxicities attributed to megestrol acetate included episodes of chills, appetite stimulation/weight gain, vaginal bleeding, and carpal tunnel syndrome symptoms. CONCLUSIONS: A substantial proportion of patients continue to use megestrol acetate for periods of up to 3 years or longer with continued control of hot flashes. This treatment appears to be relatively well tolerated.

Breast Neoplasms↗