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)

Amonafide (benzisoquinolinedione, NSC 308847) is a new synthetic imide antineoplastic agent with DNA intercalative properties that has been evaluated in a phase I clinical trial. The drug was administered as a single intravenous (IV) infusion over 30 to 120 minutes repeated every 28 days. Ninety-five courses of therapy at doses ranging from 18 to 1,104 mg/m2 were administered to 38 patients with refractory solid tumors. Granulocytopenia was dose limiting. Leukopenia was seen in 13 of 31 courses at doses of 690 mg/m2 or greater. Life-threatening granulocytopenia (less than or equal to 250 microliters) was noted in 1/6 patients treated at 800 mg/m2, 1/8 patients treated at 918 mg/m2, and 2/5 patients treated at 1,104 mg/m2. No definite relationship between myelotoxicity and prior treatment status was noted. Rate-of-infusion dependent, nonhematologic toxicities included diaphoresis, flushing, dizziness, and tinnitus, all of which were ameliorated by increasing the duration of drug infusion to 120 minutes. In addition, nausea and vomiting (grades 1 and 2) were seen in 29/56 courses at doses greater than or equal to 519 mg/m2, but were easily controlled by phenothiazine antiemetics. Amonafide plasma and urine concentrations were determined by high-pressure liquid chromatography (HPLC). Plasma concentrations declined biexponetially with a terminal harmonic mean terminal half-life (t 1/2) of 5.5 h. The mean apparent volume of distribution at steady-state and total body clearance were 532 L/m2 and 84 L/h/m2, respectively. Less than 5% of the total dose of amonafide was excreted unchanged in the urine. Antitumor activity has been noted in one patient with non-small-cell lung cancer (one complete response exceeding 29 months duration) and in one patient with prostatic cancer (complete pain relief and improvement in bone scan for 9 months). The recommended dose for phase II trials with this schedule of amonafide is 918 mg/m2 with dose escalation to amonafide is 918 mg/m2 with dose escalation to myelotoxicity.
J Clin Oncol 1989 Sep
PMID:Phase I clinical investigation of amonafide. 254 5

The metabolic response of the rat liver to flushing and reflushing with Marshall's solution at pH 7.2 or pH 7.8 has been studied by 31P nuclear magnetic resonance spectroscopy. The changes in intracellular pH, inorganic phosphate, ATP and phosphomonoesters have been determined from the 31P spectra. We show that the intracellular pH at any stage of the flushing protocol is largely independent of the pH of the medium when using these solutions. However, we demonstrate that there are differences between the efficiency of the two solutions in respect of the rates of hydrolysis of ATP and accumulation of phosphomonoesters. There were also differences in the response of the livers upon reflushing--those livers reflushed at pH 7.2 resynthesized ATP from a lower initial concentration to achieve ATP concentrations similar to those restored in livers reflushed at pH 7.8. These trends were mirrored in the responses of the phosphomonoester peaks (which contain a contribution from AMP). We conclude that short-term control of liver metabolism during hypothermia is possible by use of solutions of different pH, but that for longer-term storage, other approaches may be necessary to maintain metabolic integrity.
NMR Biomed 1989 Sep
PMID:Biochemical consequences of reflushing hypothermically-stored liver with fresh cold perfusate. Studies on rat liver using 31P NMR spectroscopy. 264 Dec 99

The purpose of this study was to evaluate the value of additive components and colloid included in the University of Wisconsin (UW) solution. Therefore, this solution was compared with a solution consisting of the basic components of the UW solution (potassium lactobionate, raffinose, phosphate buffer and MgSO4). We employed a method of measuring the amount of chromium-51-labeled erythrocyte trapped in the medullary vasculature 20 min after reperfusion of kidney grafts cold-stored for 24-48 h in either the basic UW (bUW) or the original UW (oUW) solution. The amount of trapping has been shown to correlate well with the degree of cold ischemic injury. Both hemodiluted (hct 20-27%) and normal (hct 41-45%) recipients were used. Long-term viability of grafts stored in either bUW or oUW was investigated in survival experiments and the flow rates during in situ flush-out were also measured, as well as weight changes during the storage period. The results showed no significant difference between the two solutions, regardless of ischemia time or whether hemodiluted or normal recipients were used. However, the flow rate and weight measurements showed that flushing was more rapid and kidney swelling less pronounced using oUW. Survival rates in long-term transplantation experiments were similar. It was concluded that the inclusion of a colloid improves the rheological properties of the UW solution and that the additives besides the basic components did not offer any advantage.
Transplantation 1989 Sep
PMID:Relevance of additive components of University of Wisconsin cold-storage solution. An experimental study in the rat. 278 5

The diagnostic and therapeutic potential of intravenous adenosine was studied in 64 patients during 92 episodes of regular sustained tachycardia. In 40 patients who had narrow complex tachycardias (QRS less than 0.12 s) adenosine (2.5-25 mg) restored sinus rhythm in 25 with junctional tachycardias (46 of 48 episodes) and produced atrioventricular block to reveal atrial or sinus tachycardia in 15. In 24 patients with broad complex tachycardias (QRS greater than or equal to 0.12 s) adenosine terminated the tachycardias in six patients and revealed atrial or sinus arrhythmias in four. The tachycardias persisted in 14 patients despite doses up to 20 mg, but adenosine allowed the diagnosis of ventricular tachycardia with retrograde atrial activation in two patients by producing transient ventriculoatrial dissociation. Diagnosis based on adenosine induced atrioventricular nodal block was correct in all patients with narrow complex tachycardias and in 92% of those with broad complex tachycardias, compared with correct electrocardiographic diagnoses in 90% and 75% respectively. Adenosine gave diagnostic information additional to the electrocardiogram in 25%. The response to adenosine in broad complex tachycardias identified those of supraventricular origin with 90% sensitivity, 93% specificity, and 92% predictive accuracy. Adenosine restored sinus rhythm in all patients with junctional reentrant tachycardias, but in 10 (35%) the arrhythmias recurred within two minutes. Symptomatic side effects (dyspnoea, chest pain, flushing, headache) were reported by 40 (63%) patients and, although transient, were severe in 23 (36%). There were ventricular pauses of over 2 s in 16% of patients, the longest pause being 6.1 s. Adenosine is of value in the diagnosis and treatment of narrow and broad complex tachycardias, but its use is limited by symptomatic side effects, a tenfold range in minimal effective dosage, occasional action at sites other than the atrioventricular node, and early recurrence or arrhythmia.
Br Heart J 1989 Sep
PMID:Value and limitations of adenosine in the diagnosis and treatment of narrow and broad complex tachycardias. 278 11

One hundred and seventeen episodes of supraventricular tachycardia in 50 children, including 28 infants, were treated with intravenous adenosine. Adenosine was prepared in a sterile solution of 0.9% saline (1 mg/ml) and given in incremental doses of 0.05 mg/kg every two minutes to a maximum of 0.25 mg/kg. Ninety of the 117 episodes were terminated. This included 88 of the 102 episodes of junctional tachycardia (79 of the 92 episodes of atrioventricular reentry tachycardia, seven of the eight episodes of atrioventricular nodal reentry tachycardia, and both of the episodes of long R-P' tachycardia). Only one of four episodes of His bundle tachycardia and one of the eight episodes of ectopic atrial tachycardia were terminated. None of the three episodes of atrial flutter were terminated. Side effects were frequent but mild and included transient complete atrioventricular block (less than 6 s), sinus bradycardia (less than 40 s), ventricular extrasystoles, flushing, nausea, headache, and respiratory disturbance. Reinitiation (within 5 s) of supraventricular tachycardia occurred in 13 of the terminated episodes. Although reinitiation limited its clinical efficacy in some patients, intravenous adenosine offered a safe and efficient method of rapid termination of most episodes of supraventricular tachycardia and in some cases facilitated diagnosis of the mechanism.
Br Heart J 1989 Sep
PMID:Efficacy and safety of adenosine in the treatment of supraventricular tachycardia in infants and children. 278 12

We have identified PAF in the blister fluid from a patient with bullous mastocytosis, a rare form of mast-cell disease. We have found a novel endogenous inhibitor of platelet aggregation which obscured the presence of the PAF in unprocessed blister fluid and in ethanol or lipid extracts. The PAF was characterized by the demonstration of chromatographic, mass spectral and biological properties identical to those of authentic PAF. Thus this is the first demonstration of PAF in biological fluid from a patient with mastocytosis. High levels of immunoreactive prostaglandin D2 (PGD2) and histamine were also present in the blister fluid. The interaction between PAF and the inhibitor of platelet aggregation in patients with systemic mastocytosis may provide an explanation for some of the manifestations of the disease, in particular the episodic hypotension, cutaneous flushing and pallor.
Clin Exp Immunol 1989 Sep
PMID:Occurrence of platelet-activating factor (PAF) and an endogenous inhibitor of platelet aggregation in diffuse cutaneous mastocytosis. 280 9

We have reviewed data pertinent to three tumor syndromes that derive from overproduction of three GEP peptide hormones. The clinical syndrome of somatostatin excess remains well defined with diabetes, diarrhea, steatorrhea being predominant features. With the availability of assays and increasing awareness, more cases are being diagnosed in the intestine and these differ somewhat in their presentation with cholecystitis, GI bleeding, or a mass as the cardinal features. An unusual association with MEN II pheochromacytoma and neurofibromatosis is emerging. PPomas remain enigmatic. Although diarrhea is a feature, these tumors are usually silent and present with hypatomegally, abdominal pain, and jaundice because of the large size and malignant nature. Neurotensinomas remain rare and truly difficult to separate from the symptom complex produced by VIP excess. Edema, hypotension, cyanosis and flushing should alert one to the possibility of a neurotensin-secreting tumor.
Semin Oncol 1987 Sep
PMID:Somatostatinomas, PPomas, neurotensinomas. 282 62

Forty-one children, aged 1 to 5 years, who accidentally ingested levothyroxine sodium were studied. Symptoms possibly associated with the ingestion occurred in 11 patients (27%). These symptoms (tachycardia, hyperactive behavior, fever, vomiting, diarrhea, diaphoresis, and flushing) were categorized as minor and all resolved without treatment. Because observed effects were generally mild and often unrelated to either estimated amounts of hormone consumed or serum thyroxine levels, a conservative approach to patient treatment is recommended in cases of levothyroxine ingestion in children.
Am J Dis Child 1987 Sep
PMID:Clinical effects of accidental levothyroxine ingestion in children. 288 6

Levels of beta-endorphin-like immunoreactivity (beta END-LI) in uterine secretions were studied in pseudopregnant and ovariectomized gilts treated with ovarian steroids. Pseudopregnancy was induced in 7 gilts by daily injection of estradiol valerate (5 mg/day) between days 11 and 15 of the estrous cycle. Between days 60 and 90 of pseudopregnancy, uterine secretions were collected by flushing the uterus with 0.9% saline. Uterine flushings were extracted with a Sep-Pak C-18 column and assayed for beta END-LI by a specific RIA. The RIA cross-reacted only with beta-lipotropin (15%). Significant amounts of total immunoreactive beta END-LI were detected in the uterine flushings. The inhibition curve for extracts was parallel to the standard END inhibition curve. Extracted uterine flushings were applied to a Sephadex G-50 column. Three peaks of immunoreactive beta END-LI were detected. One peak eluted at the void volume. The second peak eluted at a Kav of 0.21, which was near the Kav of a lipotropin standard (0.23). The highest peak (Kav = 0.53) eluted similar to standard END (Kav = 0.51). In the second experiment, 12 gilts were ovariectomized on day 4 of the estrous cycle and randomly assigned to 4 groups of 3 gilts each. Each group received 1 of the following daily injections: vehicle (corn oil), 0.1 mg 17 beta-estradiol (E2), 200 mg progesterone (Prog), or a combination of E2 and Prog (E2 + Prog). After treatment for 30 days, beginning on the day of ovariectomy, the uterine flushings were assayed for beta END-LI and total protein. Treatment with Prog increased (P less than 0.05) total beta END-LI 532% (12.4 ng) compared to corn oil treatment (2.3 ng), and levels were significantly higher than with E2 (2.9 ng) or E2 + Prog treatment (5.1 ng). Opiate receptor assay showed that extracts of uterine flushing had a displacement curve parallel to that of standard porcine beta END. Results suggest that significant amounts of immunoreactive beta END-LI are present in uterine secretions of gilts and that the accumulation of beta END-LI is influenced by ovarian steroids.
Endocrinology 1987 Sep
PMID:Beta-endorphin in uterine secretions of pseudopregnant and ovariectomized, ovarian steroid-treated gilts. 295 91

Twenty-five hypercholesterolaemic patients from three centres in the UK were investigated in an open study of the efficacy and side effects of niceritrol. Five patients dropped out of the study at an early stage and had insufficient data for analysis. There were 13 males and 7 females (mean age 49.2 years, range 18-69). Fourteen patients had heterozygous familial hypercholesterolaemia, and six polygenic hypercholesterolaemia. Niceritrol was started at a dose of 750 mg/day and this was increased at weekly intervals over 4 weeks to the maximum tolerated dosage up to 3 g/day. This was then maintained for a further 8 weeks. There were statistically significant decreases in total plasma cholesterol, total triglyceride, LDL cholesterol and VLDL triglyceride; HDL cholesterol remained unchanged after 12 weeks of treatment (Wilcoxon matched pairs, signed ranks test). The 14 patients with familial hypercholesterolaemia showed a 13.9% fall in total cholesterol and a 19.8% fall in LDL cholesterol. All patients reported flushing and some had gastrointestinal symptoms but 19 would have been prepared to continue with the therapy at doses up to 3 g/day. Thus niceritrol has been found to be beneficial in the treatment of both familial and polygenic hypercholesterolaemia.
Postgrad Med J 1988 Sep
PMID:Clinical and laboratory responses to niceritrol in the treatment of hypercholesterolaemia. 307 43


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