Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diethyldithiocarbamate (DDTC), a heavy metal-chelating agent, has been shown to decrease cisplatin (CP) toxicity in preclinical studies. This phase I dose-escalation study was undertaken to investigate DDTC as a chemoprotector in patients with advanced cancer. Thirty-five courses of CP in doses ranging from 120 to 160 mg/m2 were given intravenous (IV) bolus to 19 patients. DDTC at 4 g/m2 was infused over 1 hour, starting 45 minutes after CP. There was minimal nephrotoxicity with a mean creatine clearance of 99 mL/min +/- 4 pretreatment and 86 mL/min +/- 4 on day 21. Two courses were associated with a WBC count less than 2,000/mm3 and one course with a platelet count of 15,000/mm3. Two patients had grade 2 neurotoxicity. Hearing loss occurred in 11 patients: five greater than or equal to 20 dB, five greater than or equal to 40 dB, and one greater than or equal to 60 dB. All patients who received cranial irradiation had ototoxicity compared with 43% of those without radiation (P less than .05). All patients experienced toxicity during the DDTC infusion, including hypertension, flushing, diaphoresis, agitation, and local burning. We conclude that DDTC can protect against CP nephrotoxicity at doses up to 160 mg/m2. Ototoxicity became the dose-limiting factor.
J Clin Oncol 1990 Sep
PMID:Modification of cisplatin toxicity with diethyldithiocarbamate. 164

Drug therapy should be reserved for patients with marked total cholesterol elevation not amenable to dietary measures. While current guidelines suggest that bile acid sequestrants, such as cholestyramine and colestipol, are first-line drugs for the treatment of hypercholesterolemia, recent studies suggest that lovastatin is a safe, more potent alternative. Gemfibrozil reduces the serum triglyceride level and raises the high-density lipoprotein (HDL) cholesterol level, but has only a moderate effect on the serum cholesterol level. Nicotinic acid lowers serum low-density lipoprotein (LDL) cholesterol and triglyceride levels and raises serum HDL levels, but its use is limited because of troublesome side effects, notably a flushing reaction. Probucol lowers both serum LDL and HDL levels and is a second-line agent for the treatment of hypercholesterolemia.
Am Fam Physician 1990 Sep
PMID:Comparison of cholesterol-lowering regimens. 205 39

1. Aspects of quality of life (symptoms, psychological well-being and activity) were evaluated by self-administered questionnaires in a 4 month randomised double-blind trial of titrated doses of verapamil slow release (n = 41) compared with nifedipine retard (n = 40). An untreated diastolic blood pressure of 95-115 mm Hg was required for inclusion in the trial. 2. The mean age in both groups was 55 years. A significant difference between the two drugs was found in the average reporting of symptoms with an increase on nifedipine (P less than 0.01). The reporting of swollen ankles and flushing (P less than 0.05) increased on nifedipine, and nocturia (P less than 0.05) increased on verapamil. Measures of psychiatric morbidity tended to improve on verapamil and deteriorate on nifedipine. Only the change in cognitive function was significant between the drugs, being worse on nifedipine (P = 0.05). 3. There was no difference between the two groups in the fall in diastolic blood pressure (average 18 mm Hg on nifedipine and 17 mm Hg on verapamil). There was a significantly greater fall in systolic blood pressure on nifedipine (23 mm Hg) compared with verapamil (13 mm Hg) (P less than 0.01). 4. The two drugs differed in their effects on measures of quality of life. The improvements in symptomatic complaints and psychological well-being on verapamil may have been due to inclusion in a trial, although we cannot exclude the possibility of a drug effect. Conversely the increase in symptoms and self-assessed cognitive impairment on nifedipine were considered to be side-effects of the drug.
Br J Clin Pharmacol 1990 Sep
PMID:A comparison of verapamil and nifedipine on quality of life. 222 15

The present study was performed in order to explore the influence of ova present within rat oviducts on: a) tubal spontaneous motility and b) oviduct prostaglandin production. It was found that the isometric developed tension (IDT) of tubes isolated from proestrous rats (preovulatory oviducts) was significantly higher (P less than 0.01) than the IDT of tubes from rats at estrus and at metestrus (postovulatory oviducts). After flushing the oviducts with KRB solution (i.e., after removing existing ova) the IDT of the oviducts obtained from estrous rats increased significantly (P less than 0.01), whereas the IDT of tubes isolated from proestrous rats (i.e., preparations without ova) was not modified. On the other hand, isolated tubes containing their corresponding ova released into the suspending solution significantly more PGE1 than PGE2 or PGF2 alpha (P less than 0.005). It was particularly interesting to find that after flushing the oviducts, tissue production of PGE1, PGE2 and PGF2 alpha was similar. Finally, when dose response curves for PGE1 and for PGE2 on the spontaneous contractions of oviducts isolated from rats at proestrus, estrus and metestrus were constructed, both PGs evoked an inhibitory inotropic action. The ED50 for PGE1 in tubes from estrous rats was significantly smaller (P less than 0.01) than that for metestrous animals but significantly greater (P less than 0.01) than that observed in oviducts from proestrous rats. The ED50 for PGE2 did not change in the different tested periods of the sex cycle. Results reported herein suggest the possibility that the ova present within rat oviducts, may influence their own transport along the tubes by modifying the amount of prostaglandins produced by the oviducts or via their own prostaglandin synthesis.
Prostaglandins Leukot Essent Fatty Acids 1990 Sep
PMID:Influence of ova within rat oviducts on spontaneous motility and on prostaglandin production. 225 Dec 92

Prostacyclin (PGI2) is known to cause vasorelaxation and inhibit platelet aggregation by receptor-mediated mechanisms. While cyclic (c)AMP is known to act as a second messenger for platelet aggregation, vasorelaxation by hyperpolarization has been described only recently and may provide an explanation, in addition to stimulation of cAMP, for the PGI2 mechanism of action on blood vessels. When PGI2 is infused into healthy volunteers it reduces blood pressure only at infusion rates that also cause significant side effects, primarily nausea, emesis, flushing, diphoresis and restlessness. In hypertensive patients blood pressure responses are complex and are influenced to some extent by secretion. PGI2 stimulates renin secretion by a direct effect on the juxtaglomerular apparatus, and also has an indirect effect by activating the sympathetic nervous system. Thus it is useless as an antihypertensive agent even apart from its debilitating side effects. Vascular PGI2 is synthesized endogenously by both the endothelial cells and the muscularis of arteries. While the endothelial cells undoubtedly synthesize larger amounts of PGI2, the muscularis comprises a much larger tissue mass so that the overall synthesis is about equally distributed between the endothelial and muscle cells. In patients with pregnancy-induced hypertension and some patients with essential hypertension, endogenous synthesis of PGI2 has been evaluated by measuring 2,3-dinor-6-keto-PGF1 alpha and has proved to be defective. Some drugs (cicletanine, thiazides, propranolol) have been shown to stimulate PGI2 synthesis, and inhibition of cyclooxygenase has been shown to abolish their antihypertensive effects. Whether stimulation of PGI2 synthesis affects the antihypertensive efficacy of these drugs is not yet known.
J Hypertens Suppl 1990 Sep
PMID:Prostacyclin in hypertension. 225 88

A 57-year-old man took 30 x 20 mg nifedipine retarded release tablets. He developed hypotension, tachycardia and flushing, but remained in sinus rhythm. The concentration of nifedipine 10 h after overdose was 604 micrograms 1-1, and of the M-I metabolite 110 micrograms 1-1. Log concentration time curves were linear from 10-72 h for nifedipine, with a half-life of 7.5 h; and for M-I with a half-life of 8.2 h. On this evidence, oral absorption of nifedipine retarded release is complete by 10 h. There was no evidence of saturation of nifedipine or M-I metabolism, even at concentrations ten times above the therapeutic concentration.
Hum Exp Toxicol 1990 Sep
PMID:Pharmacokinetics and toxic effects of nifedipine in massive overdose. 226 Dec 44

The plasma concentrations of various tachykinins were measured before and during flushing episodes in 16 patients with metastatic carcinoid tumors. The flushing attacks were induced by iv injection of pentagastrin or ingestion of food or alcohol. Tachykinins, such as neurokinin A (NKA) and neuropeptide K (NPK), increased 2-fold during flushing episodes in 12 patients, and the plasma concentrations of substance P increased to a varying extent in 3 patients. Chromatographic analysis of plasma samples taken before and during flushing episodes in 2 patients indicated the presence of individual spectra of tachykinins. In addition, the plasma concentration of tachykinin [TKLI(K12)], using an assay that detects NKA, NPK, kassinin, eledoisin, and NKB, but not substance P and physalaemin, and the urinary excretion of 5-hydroxyindole acetic acid (5-HIAA) were measured in 20 patients with midgut carcinoid tumors before and during treatment with human leucocyte interferon. The overall changes in the 2 tumor markers were concordant in 18 of the 20 patients. Thus, the Spearman correlation coefficient between the percent changes in urinary 5-hydroxyindole acid excretion and plasma TKLI(K12) was 0.54 (P less than 0.001). The patients who had a decrease in the tumor markers also had a decrease in flushing episodes and diarrhea. Plasma TKLI(K12) is a convenient tumor marker for the diagnosis and follow-up of patients with carcinoid tumors of midgut origin. The combined use of both tumor markers strengthens the diagnosis and may improve the evaluation of response during treatment.
J Clin Endocrinol Metab 1986 Sep
PMID:Tachykinins in carcinoid tumors: their use as a tumor marker and possible role in the carcinoid flush. 242 99

We studied the effects of a long-acting analogue of somatostatin (SMS 201-995, Sandoz) in 25 patients with histologically proved metastatic carcinoid tumors and the carcinoid syndrome. This drug was self-administered by subcutaneous injection at a dose of 150 micrograms three times daily. Flushing and diarrhea associated with the syndrome were promptly relieved in 22 patients. All 25 patients had an elevated 24-hour urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA) (mean, 265 mg per 24 hours; range, 14 to 1079), which served as an objective indicator of disease activity. Eighteen of the 25 patients (72 percent) had a decrease of 50 percent or more in their urinary 5-HIAA levels, as compared with the pretreatment values. The median duration of this biochemical response was more than 12 months (range, 1 to greater than 18). Since no serious toxicity was observed, we conclude that SMS 201-995 may be appropriate for use as early therapy in patients with symptoms due to the carcinoid syndrome who have not responded to simpler measures.
N Engl J Med 1986 Sep 11
PMID:Treatment of the malignant carcinoid syndrome. Evaluation of a long-acting somatostatin analogue. 242 48

To determine the effects of reversible medical castration on prostatic size and symptoms we treated 15 patients with benign prostatic hypertrophy with a long-acting GnRH analog, leuprolide (1 mg/day sc), for a minimum of 4 months. The men's serum testosterone, dihydrotestosterone, and estradiol concentrations fell to very low levels within 4-6 weeks after the initiation of treatment. Transrectal ultrasonography of the prostate demonstrated an average shrinkage of 40% after 4 months of treatment (n = 15) and 46% after 6 months of treatment (n = 11). All 15 men had improvement in urinary flow and, to a lesser extent, in nocturia and frequency. The side-effects of the therapy were decreased potency and flushing. The most dramatic improvement occurred in 4 of the 5 men who had complete urinary obstruction before treatment. One man had a suprapubic cystotomy tube removed during the fifth treatment month. Two other men who had Foley catheters before treatment are voiding well without catheters since their third treatment month. Another man who had a very large prostate (300 g) before treatment had one successful voiding trial, although he still has a suprapubic cystotomy tube. One man decided to stop treatment after 6 months. Two months later his hormone values and prostate size had returned to pretreatment levels. One man treated during the fourth and fifth months with fluoxymesterone in addition to leuprolide had regrowth of his prostate while receiving this androgen. We conclude that leuprolide treatment of men with benign prostatic hypertrophy results in shrinkage of prostatic size and concomitant improvement in the obstructive symptoms of prostatism. The prostatic shrinkage reverses when treatment is discontinued or combined with androgen.
J Clin Endocrinol Metab 1989 Sep
PMID:Effect of long-acting gonadotropin-releasing hormone analog (leuprolide) therapy on prostatic size and symptoms in 15 men with benign prostatic hypertrophy. 247 65

Nineteen patients with histologically verified midgut carcinoid tumours and liver metastases were included in a prospective study with daily recombinant human alpha 2b interferon injections of 5 million IU subcutaneously for 1 year. All had as much as possible of the primary tumour removed at laparotomy. Whenever technically possible (in seven cases), an embolization of the hepatic arteries was performed before interferon start. The response rate of the combined embolization and interferon treatment (n = 7) was 86% after 1 year, as judged from either a 50% reduction in excretion of 5-hydroxy-3-indoleacetic acid in the urine or a 50% reduction in the area of the largest liver metastasis as evaluated by computed tomography. All patients experienced an improvement in diarrhoea and/or flushing. When interferon was given alone (n = 12), 40% responded on the basis of objective criteria (50% after 6 months), whereas an improvement in either diarrhoea or flushing was experienced by 70% (75% after 6 months). In this group one patient had died and one had decided to withdraw after 6 months, at which time both were responders. We conclude that interferon seems to be an effective treatment of malignant metastatic midgut carcinoid tumours and that embolization of the liver arteries seems to increase the response rate, as judged after 1 year.
Scand J Gastroenterol 1989 Sep
PMID:Treatment of malignant metastatic midgut carcinoid tumours with recombinant human alpha2b interferon with or without prior hepatic artery embolization. 247 94


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