Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033036 (APC)
10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One hundred sixty-four patients with stage III-IV epithelial ovarian carcinoma were randomized to receive cisplatin (CDDP) 50 mg/mq, doxorubicin 45 mg/mq, and cyclophosphamide 600 mg/mq (PAC) or carboplatin 200 mg/mq, doxorubicin 45 mg/m2, and cyclophosphamide 600 mg/mq (CAC). To administer equitoxic doses at each cycle, the drug dosages were adjusted according to the hematologic toxicities experienced after the previous course; 44.7% of CAC and 21.1% of PAC patients required a dosage reduction at the second course (P = .002). Neither CAC nor PAC caused any clinically relevant neuro-nephrotoxicity; however, CDDP was administered with hydration and forced diuresis, while carboplatin was administered by rapid intravenous (IV) infusion. After six cycles, response rates were superimposable: 62.5% and 66.6% for CAC and PAC, respectively; pathologic complete responses (pCRs) were 16.7% for CAC and 23.2% for PAC; among patients with more than 2 cm residual disease, PAC induced more pCRs than CAC (eight of 52 or 15.4% v one of 42 or 2.4%, P = .07). Median survivals and progression-free survivals (PFSs) were 22.6 and 13.2 months for PAC, and 23.1 and 15.5 months for CAC, respectively; these differences are not significant. In conclusion, this trial demonstrates that equitoxic doses of PAC or CAC result in a similar response rate, PFS, and survival.
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PMID:Carboplatin, doxorubicin, and cyclophosphamide versus cisplatin, doxorubicin, and cyclophosphamide: a randomized trial in stage III-IV epithelial ovarian carcinoma. 206 62

Picture Archive and Communication Systems (PACS), which allow the electronic acquisition, storage, transportation, and viewing of medical images, hold the eventual promise of reduced costs, improved image-management logistics, and ultimately, improved patient care. But at what point in the future will PACS really cost less than film-based image management for a given hospital size; and how are these costs affected by the choice of the digital communication network? To address these questions, a static differential cost model has been constructed. PAC systems based on two high-speed networks (less than 150 megabytes per second Mbps) and two low-speed networks, as well as film, were considered for five different sized hospitals (ranging from 15,000 to 125,000 procedures per year) and two time periods (1995 and 2000). PACS equipment was assumed to have a payoff of five years. The model considered all capital and supply costs and personnel costs for the PACS and for film storage and retrieval. It did not consider any possible cost savings from logistics improvement likely to result from the adoption of a PACS. Based on the assumptions outlined, high-speed-network PACS are less costly than those based on low-speed networks for all scenarios considered. Further, even though all possible PACS cost savings were not considered, high-speed network PACS appear to be less costly than film for hospitals larger than 60,000 procedures in 1995 and larger than 15,000 in 2000, while low-speed-network PACS should cost less than film for 60,000 and 30,000 procedure hospitals in 1995 and 2000 respectively.
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PMID:A cost analysis of film image management and four PACS based on different network protocols. 209 9

Picture archiving and communication systems (PACS) are seen as an expensive application of computer technology in diagnostic medicine. They are, admittedly, an important expansion of medical informatics into the management of images, but the cost of such systems is not easily justified. Analysis of published data shows that high technology equipment has not significantly contributed to the alarming increase in health care cost in the United States. Furthermore, within the new reimbursement scheme for Medicare procedures radiology costs amount only to less than 5%. The paper gives an analysis of where high cost in PACS is concentrated and suggests ways of justifying the expense of a PAC system.
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PMID:PACS cost justification: an industry perspective. 211 14

To assess the potential role of the lipoxygenase (LO) pathway in the vasculature in an angiotensin II (ANG II)-dependent model of hypertension, we investigated the effect of LO pathway inhibition on blood pressure in the two-kidney, one-clip (2K,1C) Goldblatt hypertensive rat. The development of renovascular hypertension in 2K,1C rats was attenuated by oral administration of phenidone (Phe, 60 mg.kg-1.day-1), a nonselective LO inhibitor, throughout the 3 wk of observation after renal artery constriction. In contrast, the same treatment protocol had no effect on the evolution of hypertension in the deoxycorticosterone acetate-salt rat, which is considered to be an ANG II-independent form of hypertension. The hypotensive effect of Phe was not associated with changes in plasma renin or aldosterone concentration (PRC and PAC, respectively). In vitro synthesis of 12-hydroxyeicosatetraenoic acid (12-HETE) by aortic segments was increased in 2K,1C hypertensive rats compared with sham-operated rats. In addition, the synthesis of 12-HETE was suppressed by the in vitro addition of Phe (10(-4) M) to aortic-segment incubates obtained from 2K,1C rats and sham-operated rats. Acute administration of Phe (30 or 60 mg/kg) in 2K,1C hypertensive rats produced a rapid and sustained decrease in mean blood pressure (MBP). This decrease in MBP was accompanied by a brisk rise in PRC and PAC. In contrast, bolus administration of indomethacin, a selective cyclooxygenase inhibitor, did not affect MBP, PRC, or PAC.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of lipoxygenase pathway reduces blood pressure in renovascular hypertensive rats. 212 26

Clonidine, an agonist of central alpha-2-adrenergic receptors, reduced the peripheral sympathetic activity. With regard to the mutual pathophysiological relationship of blood pressure regulating mechanisms, the authors wanted to find out whether after clonidine administration, in addition to the known suppression of catecholamine levels (CA), also changes in the concentration of other pressor and depressor humoral substances will occur. They investigated therefore in 15 patients with essential hypertension (EH) and in three patients with pheochromocytoma the urinary excretion of free noradrenaline (NA), adrenaline (A) and dopamine (DA), the plasma renin activity (PRA), the aldosterone concentration (PAC) and atrial natriuretic factor (ANF) in plasma, using radioimmunoanalysis, always before and 24 hours after clonidine administration (Haemiton retardR) by the oral route. Its administration led in patients with EH to a decline of NA and DA. On the other hand, in pheochromocytoma their urinary excretion did not change in an unequivocal way, and when it declined, never normal NA and DA levels were reached. A excretion remained unaltered in both groups of patients. The drop of PRA after clonidine as a result of the drop of peripheral adrenergic activity was not associated with an expected parallel drop of PAC but by its rise. This effect can be explained by a reduction of the tonic inhibition of PAC output when the DA level declines. The rise of ANF after clonidine administration will be the subject of subsequent investigations. It cannot be ruled out that this effect is due to the direct action of clonidine on alpha receptors in the heart.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The effect of clonidine on humoral factors in patients with arterial hypertension]. 214 Feb 96

The local application of (-)sulpiride, 200 ng side-1, into the nucleus accumbens produced a suppression of conditioned avoidance behavior in male rats, 10 and 90 min after injection. The decrease in avoidance behavior was accompanied by a decrease in motor activity, as evidenced by changes in the number of intertrial crosses. When injected into the dorsolateral neostriatum, or the amygdala, (-)sulpiride produced a suppression of conditioned avoidance behavior at the 90-min time interval only. Considering diffusion from the injection site, as indicated by an increase in local dopamine turnover [(DO-PAC + HVA) DA-1], the effects obtained in the dorsolateral neostriatum, and possibly also the amygdala, 90 min after injection could be due to diffusion to the nucleus accumbens. The local application of (-)sulpiride into the posterior neostriatum, or into the prefrontal cortex, produced no statistically significant effect on conditioned avoidance behavior 10 or 90 min after injection. It is concluded that the performance of conditioned avoidance behavior in the rat is critically dependent on an intact dopaminergic neurotransmission in the nucleus accumbens or adjacent areas of the ventral striatum.
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PMID:Suppression of conditioned avoidance behavior by the local application of (-)sulpiride into the ventral, but not the dorsal, striatum of the rat. 214 58

The authors investigated dynamic changes and the interaction of the plasma renin activity (PRA), plasma aldosterone (PAC), i.e. the main representatives of sodium retaining systems, and of the atrial natriuretic factor (ANF) the decisive natriuretic substance in acute expansion of the extracellular volume (ECV) by infusion of two litres of saline in six controls, seven patients with essential hypertension and liver cirrhosis without ascites (6 patients) and with ascites (6 patients). The expansion evoked controversial changes of these systems. It led to a rise of ANF and suppression of PAC and PRA. Although ANF rose after infusion to the roughly similar range (12.4 to 15.7 pmol/l), the natriuretic response to expansion differed significantly in different groups of patients. It was most marked in hypertonic subjects (517.2 to 93.2 mumols/min) and practically zero in ascitic liver cirrhosis (54.2 +/- 44.2 mumols/min). The explanation of this finding may be the persistence of high activity of the renin-angiotensin-aldosterone system despite its partial inhibition by infusion of saline in cirrhosis of the liver (PRA 1.69 +/- 0.66 nmols/l/hr., PAC 1.12 nmol/l). For the renal response to acute expansion of the ECV thus not only the absolute plasma concentration of ANF is decisive but also its ratio to the activity of the sodium retaining renin-angiotensin-aldosterone system.
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PMID:[Mutual interaction of the renin-angiotensin system and the atrial natriuretic factor in the renal response to acute volume loading]. 214 4

In the ventrolateral medulla oblongata, clonidine binds not only to alpha 2-adrenergic receptors but also to a novel class of nonadrenergic sites that are specific for imidazoles. Since clonidine has direct actions on the kidney, we sought to determine whether imidazole binding sites could be detected in renal cell membranes. Adrenergic agents having an imidazole ring, like clonidine, completely displaced the specific binding of the high-affinity clonidine analog 3H-p-aminoclonidine (3H-PAC) to kidney membranes. Nonimidazole adrenergic agents inhibited 3H-PAC binding by only 75%, indicating that the remaining 25% of the sites were nonadrenergic. Cimetidine, an imidazole compound lacking adrenergic potency, showed a high affinity for approximately 25% of the sites. 3H-PAC binding to imidazole sites was high-affinity (KD = 11 +/- 3 nmol/L) and saturable (Bmax = 41 +/- 10 fmol/mg protein). Like clonidine, an endogenous clonidine-displacing substance (CDS) completely inhibited 3H-PAC binding to renal cortex membranes. Quantitative receptor autoradiography revealed that imidazole receptors exhibited a specific regional distribution within the kidney that was unique, and distinct from that of alpha 2-adrenergic receptors. We conclude that clonidine binds to specific imidazole sites in the renal cortex of the rat and that CDS may be the endogenous ligand at these sites. Thus, in addition to their role in central nervous system control of arterial pressure, imidazole receptors may be involved in the regulation of renal function.
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PMID:Characterization and visualization of clonidine-sensitive imidazole sites in rat kidney which recognize clonidine-displacing substance. 215 3

The benzodiazepine (BZ) recognition sites on the gamma-aminobutyric acid receptor/chloride ionophore complex have been suggested to be involved in the modulation of mesoprefrontal dopamine (DA) neurons. We have examined further the effects of different classes of BZ receptor ligands on DA metabolism in the prefrontal cortex. The anxiogenic inverse agonist FG 7142 elevated selectively 3,4-dihydroxyphenylacetic acid (DOPAC) levels and DO-PAC/DA ratio in the prefrontal cortex in a dose- and time-dependent manner. The activating effect was not, however, observed in any other mesocortical, mesolimbic or nigrostriatal DA terminal fields examined. Pretreatments with BZ agonists such as diazepam, flurazepam, lorazepam and CGS 9896 and BZ antagonists such as Ro15-1788 and CGS 8216 and barbiturates such as pentobarbital, significantly antagonized the beta-carboline-induced elevation of prefrontal DOPAC levels. Furthermore, a significant correlation was found between the pharmacological profile of different BZ receptor ligands on prefrontal DA metabolism and their profiles in behavioral, electrophysiological and receptor binding studies. Agonists increased DA levels and consequently decreased DOPAC/DA ratio in the prefrontal cortex. Inverse agonists, on the other hand, significantly elevated prefrontal DOPAC levels and DOPAC/DA ratio in a dose-dependent manner. Antagonists such as Ro15-1788 and CGS 8216, at low doses, did not alter mesoprefrontal DA metabolism, but at higher doses did elevate DOPAC/DA ratio in the prefrontal cortex.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Modulation of mesoprefrontal dopamine neurons by central benzodiazepine receptors. I. Pharmacological characterization. 215 1

Half the rats fed a high-energy diet develop diet-induced obesity (DIO); the remainder are diet-resistant (DR). Since alpha-adrenoceptors modulate both food intake and body weight, this study was conducted to identify potential differences in brain alpha-receptor binding which might predispose some animals to become DIO (DIO-prone) and others DR (DR-prone) when fed a high energy diet. DIO-prone rats can be prospectively identified by high and DR-prone rats by a low plasma norepinephrine (NE) response to i.v. glucose. Here 28 chow-fed rats were tested for glucose-induced NE release and the 6 highest and 6 lowest plasma NE responders were identified as being most likely to be DIO- and DR-prone, respectively. Binding to brain alpha-adrenoceptors was studied in these 12 rats by receptor autoradiography using 1 nM [3H]prazosin (PRZ; alpha 1-) and 1 nM [3H]paraminoclonidine (PAC; alpha 2-). There were no differences in [3H]PRZ binding in any of 18 brain areas examined. However, DIO-prone [3H]PAC binding was only 14-39% of DR-prone levels in 9 areas including 4 amygdalar nuclei, the lateral area, dorso- and ventromedial nuclei of the hypothalamus, median eminence and medial dorsal thalamic n. Although it is unclear whether this widespread decrease in [3H]PAC binding implicates brain alpha 2-adrenoceptors in the pathophysiology of DIO, it does correlate with a phenotypic marker (increase glucose-induced NE release) which predicts the subsequent development of DIO on a high-energy diet.
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PMID:Obesity-prone and -resistant rats differ in their brain [3H]paraminoclonidine binding. 215 28


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