Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0600142 (hot flushes)
 1,242 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Toremifene is an antiestrogen that binds strongly to estrogen receptors (ER). A total of 19 previously treated postmenopausal women with metastatic breast cancer whose performance status was good and whose ER status was positive or unknown were studied to determine the maximum tolerated dose of toremifene. Cohorts of patients received 200, 300, or 400 mg/m2 p.o. daily until relapse or unacceptable toxicity had occurred. Nausea, vomiting, and dizziness were dose-related. Three of five patients receiving 400 mg/m2 experienced moderate or severe vomiting and another developed reversible disorientation and hallucinations. Mild sweating, peripheral edema, vaginal discharge, and hot flushes were encountered at all doses. Reversible corneal pigmentation was identified in seven cases but was not of clinical importance. The pharmacokinetics of toremifene was studied weekly and in detail on day 42 using a high-performance liquid chromatographic (HPLC) assay that identified the parent compound and three active metabolites, N-desmethyltoremifene, (deaminohydroxy)toremifene, and didemethyltoremifene. Steady state was achieved at 1-3 weeks. The toremifene area under the curve and the maximal concentration were dose-dependent at high doses. The recommended phase II dose is 300 mg/m2 p.o. daily.
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PMID:Phase I clinical and pharmacokinetics study of high-dose toremifene in postmenopausal patients with advanced breast cancer. 138 61

Following a multicentre double-blind controlled trial comparing the effects of fluvoxamine and imipramine in depressed inpatients (M.D.E.) 39 patients continued on longer term treatment with maintenance of double-blind conditions (17 on fluvoxamine, 22 on imipramine). The results regarding the reasons for premature interruption of treatment show a slight advantage in favour of fluvoxamine. There were several significant differences in favour of fluvoxamine at the 20th week. The most common side-effects were hot flushes with imipramine and dizziness with fluvoxamine. Overall, despite the small number of patients, the results show a greater clinical tolerance to fluvoxamine than to imipramine.
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PMID:Fluvoxamine and imipramine: results of a long-term controlled trial. 311 Feb 64

A phase I study of benzisoquinolinedione (amonafide) was conducted in 30 patients with advanced solid tumors refractory to conventional therapy. The starting dose was 10 mg/m2/day X 5 days and the highest tolerated dose was 625 mg/m2/day X 5. The daily dose was mixed in 100 ml of normal saline and infused over 30-60 minutes. The dose-limiting toxicity was myelosuppression with nadirs of blood counts reached on Day 15 and recovery by Day 21-28. Other side effects included mild nausea and vomiting, mild phlebitis, skin rashes, and alopecia in some patients. A majority of the patients experienced dizziness, tinnitus, and hot flushes occurring predominantly at the higher dose levels. These were related to the rate of drug infusion and resolved on prolonging the infusion to 60 minutes. Pharmacokinetic studies of amonafide revealed a monoexponential plasma disappearance curve with a mean half-life of 3.5 +/- 1.9 hours. The recommended dose of amonafide for phase II studies in solid tumors is 400 mg/m2/day X 5 for good-risk and 300-320 mg/m2/day X 5 days for poor-risk patients with courses repeated at 21-28-day intervals.
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PMID:Phase I clinical investigation of benzisoquinolinedione. 369 May 26

In a randomized double-blind cross-over trial, the effectiveness of lorcainide at a dosage of three times 100 mg/d by mouth was compared with that of a placebo for the treatment of subjectively disturbing stable ventricular extrasystoles (VES), using 48-hour continuous ECG monitoring. In 11 of 20 patients there was a regression in the VES rate to under 5%, in other 3 patients to under 50% of the initial values. Continuing the treatment, good therapeutic effect was still demonstrable 14 and 28 days later. However, only three patients had no side-effects. The others had sleep disturbances, hot flushes, sweating, restlessness, anxiety, dizziness, hallucinations and gastrointestinal symptoms. Lorcainide thus has a good anti-arrhythmic effect but, because of its side-effects, it should be used only in special circumstances.
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PMID:[Lorcainide in stable ventricular extrasystole. A double-blind study with 48-hour continuous ECG recording]. 620 80

double-blind cross-over study with Org OD 14 was done in 35 post-menopausal patients aged 48-69 years who had hot flushes and other associated symptoms. Patients were randomly allocated to Org OD 14 or to placebo as first treatment. Each period of treatment lasted for 6 weeks and there were no intervals between treatments. Tablets containing 2.5 mg of Org OD 14 or placebo tablets of identical appearance were supplied. Patients took one Org OD 14 tablet or one placebo tablet per day. Data on the following variables were obtained and analyzed statistically: hot flushes, sweating, dizziness, palpitation, tiredness, headache, insomnia, irritability, breathlessness, backache, loss of libido, and mood. Assessment was daily in the case of hot flushes and weekly for the other variables. Org OD 14 was statistically significantly more effective in controlling hot flushes, sweating and headache and tended to be better than the placebo tablets for the other variables.
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PMID:Double-blind cross-over study with Org OD 14 and placebo in postmenopausal patients. 666 Sep 26

A double-blind cross-over study with Org OD 14 and placebo was performed in 82 menopausal patients presenting with hot flushes and associated symptoms. Patients were randomly allocated to Org OD 14 or placebo as first treatment, and switched to placebo or Org OD 14 as second treatment. Each treatment period lasted for 16 weeks; no wash-out period was introduced. Tablets containing 2.5 mg of Org OD 14 or matched placebo tablets were supplied. Data on the following variables were obtained and analysed by the non-parametric randomization test for paired observations: hot flushes, sweating, dizziness, palpitations, fatiguability, headache, sleeplessness, irritability, breathlessness, backache and loss of libido and, in 16 patients, on circulating levels of FSH, LH, PRL, T3, T4, cortisol (F), SHBG, TBG and CBG. Twenty patients (13 placebo, 7 Org OD 14) withdrew, because their symptoms did not improve and one patient withdrew for reasons unrelated to treatment, so that 61 patients completed the study. The data demonstrated a good clinical effect and statistically significant differences in favour of Org OD 14 for hot flushes and a number of associated symptoms. Many patients reported on a general feeling of well being and a mood-elevating effect following Org OD 14. Org OD 14 significantly suppressed FSH and LH levels, while those of PRL remained unchanged. Although there was slight suppression of TBG and T4 which attained statistical significance, there was no influence on the most important parameter, T3. SHBG levels were slightly suppressed, whereas F and CBG levels were unaffected.
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PMID:Placebo-controlled cross-over study of effects of Org OD 14 in menopausal women. 675 12

Panic disorder is a chronic illness that affects at least 3 percent of the population. Panic disorder is associated with significant morbidity and an increased risk of suicide. Patients generally present with multiple somatic and psychologic complaints, including heart palpitations, chest pain, tremor, shortness of breath, choking, nausea or abdominal distress, dizziness, derealization, fear of losing control or going crazy, fear of dying, paresthesias, chills or hot flushes, headache, diarrhea, insomnia, chronic fatigue, anxiety and depression. To make the correct diagnosis, these symptoms must be evaluated carefully since they also occur with serious cardiovascular, pulmonary, endocrinologic and neurologic disorders. Many effective treatments are available, including tricyclic antidepressants, selective serotonin reuptake inhibitors, monoamine oxidase inhibitors, benzodiazepines such as alprazolam and clonazepam, and psychotherapy.
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PMID:Panic disorder. 748 99

The connection between body-shape characteristics, namely distribution of subcutaneous fat, and the occurrence of psychic and somatic climacteric symptoms was investigated in 142 postmenopausal women from Eastern Austria. It was found that both psychic and somatic symptoms are significantly related to body-shape characteristics. With increasing breadth and circumference, i.e. a higher proportion of subcutaneous fat, the degree of severity of several symptoms increases, with the exception of hot flushes and sweating, dizziness, headache and palpitation. Since, in the climacteric, subcutaneous fat has a positive impact on the secretion of oestrogens and thus on climacteric symptoms, the results of the present study may be interpreted as an effect of the psychosocial stress to which corpulent women are exposed in our society because they do not fit the beauty ideal typical of our culture.
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PMID:Relations between anthropometric characteristics and degree of severity of the climacteric syndrome in Austrian women. 813 91

Three sequential oestradiol valerate (E2V) and cyproterone acetate (CPA) combinations based on 11 days of oestrogen and 10 days of oestrogen-progestogen administration were investigated during hormone replacement therapy in two prospective, double-blind randomized trials. Treatment A comprised 2 mg E2V and 1 mg CPA, treatment B, 1 mg and 0.5 mg and treatment C, 2 mg and 2 mg, respectively. During treatment A hot flushes (P < 0.0001), night sweating (P < 0.0001), depression (P = 0.0001), dizziness (P = 0.0001) and insomnia (P = 0.003) decreased significantly. The only side effect was breast tenderness, which was experienced by 18% of the women. Weight and blood pressure, thyroid, adrenal, liver and kidney functions, parathyroid hormone and vitamin D, platelets and blood cell counts did not change during the 12 months of therapy. In the women who received treatment A the menstrual flow became less abundant during the early months of treatment (P < 0.0001), the menses being scanty in around 30% of the women, while some 10% had amenorrhoea. Spotting occurred in 10-20% of the subjects. Endometrial biopsies were atrophic in 10% of the women, whereas a normal secretory phase was observed in 45% and irregular secretion in 45%. After careful analysis using visual analog scales, these findings were interpreted as indicating a high-normal progestational effect. In comparison with the pattern observed in normal menstrual cycles the women who received treatment A had a more heterogenic glandular epithelium, with more papillae, larger stromal cells, a more pronounced decidual reaction and more fibrinoid material. No cases of hyperplasia were seen. Treatment B was less effective than treatment A in relieving climacteric complaints. Irregular bleeding was troublesome in over 20% of cases and amenorrhoea occurred in 50%. Endometrial biopsies were atrophic in 57% of the women. The effectiveness of treatment C in alleviating flushes, sweating, dizziness and depression was the same as that of treatment A. The decrease in menstrual flow during the early months and the incidence of amenorrhoea (approx. 10%) and atrophic endometria (approx. 10%) were comparable. Detailed analysis revealed that C had an even stronger progestational effect than A. It was concluded that A was the treatment of choice in comparison with B and C. It proved highly effective in treating climacteric complaints, had no side effects apart from breast tenderness, provided good cycle control and induced a physiological secretory transformation of the endometrium.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Endometrial effects during hormone replacement therapy with a sequential oestradiol valerate/cyproterone acetate preparation. 838 51

In order to determine the usual dose in the first line therapy and a high dose in the second or third line therapy, a dose finding study of a novel antiestrogen NK 622 (toremifene citrate) was performed in patients (pts) with advanced or recurrent breast cancer. NK 622 was orally administered daily once for more than 8 weeks. In pts without previous drug therapy or in pts with cancer relapse after adjuvant therapy, the response rates [(CR + PR)/total] were 24.1% (7/29), 13.8% (4/29), 20.0% (1/5) and 40.0% (2/5) at doses of 40, 60, 120 and 240 mg/day, respectively. A 40 mg/day dose showed an objective response only in postmenopausal pts with estrogen receptor (ER) positive or unknown cancer. At a dose of 60 mg/day, some of the responding cases were premenopausal pts or pts with ER(-) cancer. In pts with cancer relapse during adjuvant therapy or in those with previous therapy and/or radiation, response rates were 25.0% (2/8), 0% (0/4), 13.5% (5/37) and 10.3% (4/39) at doses of 40, 60, 120 and 240 mg/day, respectively. Response was more frequent in pts with ER (+) cancer than with ER (-) cancer. The response rates in pts with previous therapy including tamoxifen (TAM) except medroxyprogesterone (MPA) were 14.3% (4/28) at a 120 mg/day dose and 6.1% (2/33) at a 240 mg/day dose. In pts with previous therapy including TAM, MPA and other antitumor agents, the rate was 18.2% (2/11) at a 120 mg/day dose. Side effects such as elevation of GOT, GPT and serum Ca level, decrease of hemoglobin, anorexia, nausea/vomiting, fatigue, dizziness and hot flush were observed. These side effects were moderate in grade and reversible. Dose dependency of side effects was not clearly observed in grade and incidence. From these results, NK 622 is expected to be a safe drug with efficacy in first line therapy at a dose of 40 mg/day and in second or third line therapy at a dose of 120 mg/day.
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PMID:[Phase II study of NK 622 (toremifene citrate) in advanced breast cancer, a multicentral cooperative dose finding study]. 842 89


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