Fish oil has been recently proposed as a possible effective treatment in inflammatory bowel disease (IBD); however, a lot of annoying side effects (ie, belching, halitosis, diarrhea, etc) affect patient compliance. We carried out a study of patient tolerance in a group of Crohn's disease (CD) patients with a new fish oil derivative consisting of 500-mg capsules of eicosapentaenoic-docosahexaenoic (EPA 40%-DHA 20%), a free fatty acid mixture (Purepa), and we also evaluated its incorporation into phospholipids, both in plasma and in red cell membranes. Five groups of 10 CD patients in remission received nine Purepa capsules daily in four different preparations (A: uncoated, B: coated, pH 5.5; C: coated, pH 5.5, 60 min time release; D: coated, pH 6.9) and 12 × 1-g capsules daily of a triglyceride preparation (Max-EPA, EPA 18%-DHA 10%), respectively. We coated three of the four Purepa preparations in order to delay the release of contents in an attempt to minimize the side effects. After six weeks of treatment, the group taking Purepa capsules, coated, pH 5.5, 60 min time release (group C) showed the best incorporation of EPA and DHA in red blood cell phospholipid membranes (EPA from 0.2 to 4.4%, DHA from 3.7 to 6.3%), and no side effects were registered, whereas in all other groups side effects were experienced in 50% or more of subjects. This new preparation will make it possible to treat patients for long periods. 相似文献
Background: We performed a phase I study of a novel system of complete hepatic venous isolation and extracorporeal chemofiltration in
patients with unresectable hepatocellular carcinoma (HCC) to determine (a) whether systemic exposure to doxorubicin could
be limited after high-dose hepatic arterial infusion (HAI), and (b) the hepatic maximum tolerated dose (MTD) of doxorubicin.
Methods: Ten patients with biopsy-proven HCC were treated with 20-min HAI of doxorubicin (17 total treatments). Two patients were
treated with doxorubicin 60 mg/m2, three patients were treated at 90 mg/m2, and five patients received 120 mg/m2. A newly developed dual-balloon vena cava catheter was advanced from the femoral vein, and the balloons were inflated to
isolate and capture total hepatic venous outflow. The hepatic venous blood was pumped through extracorporeal carbon chemofilters
before return of the blood to the systemic circulation.
Results: Peak systemic doxorubicin levels were an average 85.6% lower than were peak prefilter levels (p<0.01). Because all catheters
were placed percutaneously and because the chemofiltration markedly limited systemic chemotherapy exposure, patients were
discharged 1 day after 16 of the 17 treatments. The hepatic and systemic MTD of doxorubicin in this treatment protocol was
120 mg/m2.
Conclusions: This novel system of complete hepatic venous isolation and chemofiltration limits systemic chemotherapy toxicity and will
allow use of higher doses of chemotherapeutic agents to treat HCC.
The results of this study were presented at the 46th Annual Cancer Symposium of The Society of Surgical Oncology, Los Angeles,
California, March 18–21, 1993. 相似文献
Published reports regarding the stability of morphine are at variance, especially in syringes used in patient-controlled analgesia (PCA) devices. In addition to the effects of container type and vehicle, reasons for this variation include the effect of excipients temperature and light during storage. Furthermore, the literature varies regarding the mechanisms of decomposition for morphine. To our knowledge, the stability of meperidine (pethidine) stored in plastic syringes has not been reported. The purposes of this study were to investigate the stability of morphine sulphate (1 and 5 mg/ml) and meperidine hydrochloride (5 and 10 mg/ml) in plastic syringes for use in PCA devices for a duration of 12 weeks, and evaluate the influence of light (240 foot-candies), temperature (-20, 4 and 23d?C), diluent (5% dextrose or normal saline), and drug concentration on the stability of these narcotic analgesics. Samples were taken bi-weekly for solutions protected from light and weekly for solutions exposed to light. Morphine sulphate and meperidine hydrochloride concentrations were quantified using independent, stability-indicating, high performance liquid chromatographic assays. The within-day and between-day coefficients of variation for these assays were 4% over each of the concentration ranges studied. Under the conditions of this study, it is proposed that although decomposition of morphine to its main product, pseudomorphine, can be interpreted using first-order kinetics, consecutive (to form the N-oxide) and parallel mechanisms (to form apomorphine) exist. Morphine solutions were more stable in normal saline than in 5% dextrose. SheIf-life data indicate that morphine is stable for at least 6 weeks when protected from light. Exposure to light accelerates morphine decomposition two to six-fold depending on the concentration, and the shelf-life is reduced to about 1 week in some instances. Meperidine solutions in both vehicles under all conditions had shelf-lives of at least 12 weeks. No effects of light were detected and no changes in solution colour were observed. This study illustrates that patients using PCA devices must be advised about shelf-lives as well as correct storage conditions to protect solutions of these drugs from environmental factors that may alter shelf-lives. Pharmacists should also note that other formulation factors such as: antioxidants, preservations, buffers, impurities, and the source and quality of containers, may significantly alter the shelf-lives of these drugs. 相似文献
BACKGROUND: Loss-of-function mutations in the KCNJ2 cause approximately 50% of Andersen-Tawil Syndrome (ATS) characterized by a classic triad of periodic paralysis, ventricular arrhythmia, and dysmorphic features. Do KCNJ2 mutations occur in patients lacking this triad and lacking a family history of ATS? OBJECTIVES: The purpose of this study was to identify and characterize mutations in the KCNJ2-encoded inward rectifier potassium channel Kir2.1 from patients referred for genetic arrhythmia testing. METHODS: Mutational analysis of KCNJ2 was performed for 541 unrelated patients. The mutations were made in wild type (WT) and expressed in COS-1 cells and voltage clamped for ion currents. RESULTS: Three novel missense mutations (R67Q, R85W, and T305A) and one known mutation (T75M) were identified in 4/249 (1.6%) patients genotype-negative for other known arrhythmia genes with overall incidence 4/541 (0.74%). They had prominent U-waves, marked ventricular ectopy, and polymorphic ventricular tachycardia but no facial/skeletal abnormalities. Periodic paralysis was present in only one case. Outward current was decreased to less than 5% of WT for all mutants expressed alone. Co-expression with WT (simulating heterozygosity) caused a marked dominant negative effect for T75M and R82W, no dominant negative effect for R67Q, and a novel selective enhancement of inward rectification for T305A. CONCLUSIONS: KCNJ2 loss of function mutations were found in approximately 1% of patients referred for genetic arrhythmia testing that lacked criteria for ATS. Characterization of three new mutations identified a novel dominant negative effect selectively reducing outward current for T305A. These results extend the range of clinical phenotype and molecular phenotype associated with KCNJ2 mutations. 相似文献
Background: Volatile anesthetics have protective effects against cytokine-induced injury in endothelial and vascular smooth muscle cells. The authors hypothesized that isoflurane pretreatment may trigger immediate and delayed protection that is modulated by adenosine triphosphate-sensitive potassium channels.
Methods: Human and bovine endothelial cells and rat vascular smooth muscle cells were pretreated with isoflurane (1.5% for 30 min) and then exposed to cytokines (tumor necrosis factor-[alpha], interferon-[gamma], and interleukin-[beta]) for 72 h. Cytokine exposure was initiated immediately after isoflurane pretreatment or after a delay of 1-48 h. Cell survival and viability were evaluated by trypan blue exclusion and lactate dehydrogenase release. The role of mitochondrial and cell membrane adenosine triphosphate-sensitive potassium channels, or both, were evaluated with the antagonists 5-hydroxydecanoate, HMR-1098, or glybenclamide.
Results: Immediate isoflurane pretreatment was approximately 70% effective in increasing cell survival and prevented lactate dehydrogenase release in all cell lines. However, cellular protection was completely lost if the time between isoflurane and cytokine exposure was extended to 2-12 h, depending on the cell type. Delayed protection was equal to immediate protection when the interval was extended to 12-24 h, with protection being sustained at 48 h in human endothelial and rat vascular smooth muscle cells. The immediate and delayed protection was inhibited by glybenclamide and 5-hydroxydecanoate but not by HMR-1098, whereas diazoxide, a mitochondrial adenosine triphosphate-sensitive potassium channels agonist, mimicked the time course of isoflurane-induced immediate and delayed protection in all cell lines. 相似文献
OBJECTIVES: To examine ventilatory support for the VLBW infant over the past 10 years in a single academic NICU and determine factors that predicted length of ventilation, death, and CLD. STUDY DESIGN: A retrospective cohort review of neonatal blood gases, ventilatory support, and clinical outcomes. RESULTS: From 1992 through October 2002, 6254 infants were admitted, of whom 2388 required intubation for mechanical ventilation. Of these, 837 were <1500 g at birth (VLBW) infants and 453 were less than 1000 g (ELBW). Total duration of ventilation decreased in all weight groups. Noninvasive ventilatory support increased from 20 to 55% of total ventilation from 1997 to 2002. During this same period, CLD decreased from 20 to 11% in ventilated VLBW infants. Duration of total ventilation was best predicted by birth weight, with each 100 g increment decreasing the duration of ventilation by 71 hours. Lower birth weight, male sex, and a longer total duration of ventilatory support were significant factors in predicting the occurrence of CLD. Death alone was best predicted by lower birth weight and maximum oxygen index (OI). Transported infants had significantly increased maximal OIs, durations of ventilation, and incidence of death. A total of 48% of infants with a single OI >10 either died or survived with CLD. CONCLUSIONS: Birth weight is the best predictor of duration of ventilation, and CLD is best predicted by birth weight, duration of ventilation and male sex. The increasing use of noninvasive strategies has not been associated with an observable increase in respiratory morbidity. VLBW infants with a single OI>10 may benefit from inclusion in future interventional rescue studies. 相似文献