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- Cutaneous metastasis of gastric cardia adenocarcinoma in a patient: a case report. [Journal Article]
- Int J Clin Exp Med 2014; 7(3):785-8.
A large proportion of gastric cardia adenocarcinoma (GCA) present initially in an advanced stage in China. Skin metastasis of primary GCA rarely occurs and the incidence of it is still unclear yet. Here we report one case of skin metastasis from GCA in a 58-year-old male patient who underwent gastric cardia resection in 2002 and did not undergo chemotherapy. However, he was diagnosed with anastomotic stoma adenocarcinoma by gastroscopy and histological biopsy in 2012.4. Then he underwent four cycles of "XELOX" regimen chemotherapy and the evaluation was PR. Upper gastrointestinal bleeding occurred and he was administered hemostatic therapy in 2012.9; meanwhile, he suffered from severe pains all over the body and received slow-release morphine. However, he was found to have dozens of cutaneous metastasizes in the skin of abdominal and back. Then, he underwent best supportive care and died of cachexia in 2013.5. GCA cutaneous metastasis indicates a highly invasive potential of tumors, poor chemo-radiotherapy efficacy and poor prognosis. The patient may survive just for another several months without the treatment of anti-tumor agents. Appropriate treatment may prolong patient survival.
- Signal enhancement of glucuronide conjugates in LC-MS/MS by derivatization with the phosphonium propylamine cation tris(trimethoxyphenyl) phosphonium propylamine, for forensic purposes. [JOURNAL ARTICLE]
- Drug Test Anal 2014 Apr 21.
Although chemical derivatization for signal enhancement in drug testing is most often associated with gas chromatography, it also has the potential to improve the detection of analytes poorly ionized by atmospheric pressure ionization techniques, such as electrospray ionization used in liquid chromatography-mass spectrometry. A number of acidic compounds, namely drug glucuronides (e.g. conjugates of temazepam, oxazepam, lorazepam, morphine, testosterone, epitestosterone, 5-α-dihydrotestosterone, androsterone, p-nitrophenol, and paracetamol) were successfully derivatized with tris(trimethoxyphenyl) phosphoniumpropylamine to introduce a quaternary cation functionality to the analytes. Benzodiazepine glucuronides were more specifically investigated, and following positive mode electrospray ionization mass spectrometry, average improvements to peak areas as a result of derivatization were 67-, 6-, and 7- fold for temazepam, oxazepam, and lorazepam glucuronides. Average improvements to the signal-to-noise ratios for temazepam, oxazepam, and lorazepam glucuronides were 1336-, 371- and 217-fold, respectively. The values obtained for the derivatized conjugate were also typically higher than those for the underivatized parent drug. Urine containing benzodiazepine glucuronides was also successfully derivatized. The data indicates potential for the use of charge derivatization to improve the detection of molecules with acidic functionalities by liquid chromatography-mass spectrometry (LC-MS) techniques in certain scenarios. Copyright © 2014 John Wiley & Sons, Ltd.
- Hepatic microsomal UDP-glucuronosyltransferase (UGT) activities in the microminipig. [JOURNAL ARTICLE]
- Biopharm Drug Dispos 2014 Apr 17.
The microminipig, a small minipig was bred as a novel experimental animal for nonclinical pharmacology/toxicology studies by Fuji Micra Inc. (Shizuoka, Japan). Species differences in drug metabolism between humans and the microminipig need to be elucidated in more detail in order to discuss the results of nonclinical studies. Glucuronidation catalyzed by UDP-glucuronosyltransferase (UGT) is an important pathway in the metabolism of a wide variety of compounds. The aim of the present study was to identify the characteristics of hepatic UGT activity in the microminipig and compare them to those in humans and other experimental animals. In this study, we examined in vitro UGT activities using liver microsomes from microminipigs (8 months old and 1-day-old), humans, mice, rats, dogs, monkeys, and minipigs. The glucuronides of estradiol, imipramine, serotonin, propofol, 3'-Azido-3'-deoxythymidine (AZT) and morphine, selective substrates of human UGT1A1, 1A4, 1A6, 1A9, and 2B7 (AZT and morphine), respectively, were measured using LC-MS/MS. Estradiol-3-glucuronidation activity was higher in the microminipig than in humans and the other animals. High levels of estradiol-3-glucuronidation were observed in the microsomes of 1-day-old microminipigs. Imipramine-N-glucuronidation, a distinctive conjugation by human UGT1A4, was catalyzed by microminipig liver microsomes, but not by dog liver microsomes. Although AZT-glucuronidation activity was low in the microminipig rather than that in humans, morphine-3-glucuronidation activity in the microminipig was higher than that in humans. UGT activities in the microminipig were similar to those in the minipig. The results of the present study have provided useful information to select an appropriate animal model for nonclinical studies. This article is protected by copyright. All rights reserved.
- Sedative and analgesic use on night and day shifts in a pediatric cardiovascular intensive care unit. [Journal Article]
- AACN Adv Crit Care 2014 Apr-Jun; 25(2):114-8.
The use of sedative and analgesic medications is directly linked to patient outcomes. The practice of administering as-needed sedative or analgesic medications deserves further exploration. We hypothesized that important variations exist in the practice of administering as-needed medications in the intensive care unit (ICU). We aimed to determine the influence of time of day on the practice of administering as-needed sedative or analgesic medications to children in the ICU.Medication administration records of patients admitted to our pediatric cardiovascular ICU during a 4-month period were reviewed to determine the frequency and timing of as-needed medication usage by shift.A total of 152 ICU admissions (1854 patient days) were reviewed. A significantly greater number of as-needed doses were administered during the night shift (fentanyl, P = .005; lorazepam, P = .03; midazolam, P = .0003; diphenhydramine, P = .0003; and chloral hydrate, P = .0006). These differences remained statistically significant after excluding doses given during the first 6 hours after cardiovascular surgery. Morphine administration was similar between shifts (P = .08).We identified a pattern of increased administration of as-needed sedative or analgesic medications during nights. Further research is needed to identify the underlying causes of this practice variation.
- Palliative Sedation at Home for Terminally Ill Children With Cancer. [JOURNAL ARTICLE]
- J Pain Symptom Manage 2014 Apr 18.
The presence of symptoms that are difficult to control always requires adjustment of treatment and palliative sedation should be considered.We analyzed our experience in conducting palliative sedation at home for terminally ill children with cancer during a seven-year period.We performed a retrospective analysis of medical records of children with cancer treated at home between the years 2005 and 2011.We analyzed the data of 42 cancer patients (18% of all patients); in 21 cases palliative sedation was initiated (solid tumors n=11, brain tumors (5), bone tumors (4), leukemia (1)). Sedation was introduced because of pain (n=13), dyspnea (9), anxiety (5) or two of those symptoms (6). The main drug used for sedation was midazolam; all patients received morphine. There were no significant differences in the dose of morphine or midazolam depending on the patient's sex; age was correlated with ab increase of midazolam dose (R=0.68; P=0.005). Duration of sedation (R=0.61; P=0.003) and its later initiation (R=0.43; P=0.05) were correlated with an increase of the morphine dose. All patients received adjuvant treatment; in patients who required a morphine dose increase, metoclopramide was used more often (P=0.0002). Patients did not experience any adverse reactions. Later introduction of sedation was associated with a marginally higher number of intervention visits and a significantly higher number of planned visits (R=0.53; P=0.013).Sedation may be safely used at home. It requires close monitoring and full cooperation between the family and hospice team. Because of the limited data on home palliative sedation in pediatric populations, further studies are needed.
- Dose-dependent attenuation of intravenous nalbuphine on epidural morphine-induced pruritus and analgesia after cesarean delivery. [Journal Article]
- Kaohsiung J Med Sci 2014 May; 30(5):248-53.
Epidural morphine in patient-controlled analgesia regimens controls postoperative pain well but easily induces pruritus and other epidural morphine-related side effects. With 90 pregnant American Society of Anesthesiologists physical status II females scheduled for elective cesarean delivery, the present study was designed to evaluate the efficacy and safety profile of patient-controlled antipruritus (PCP) use of intravenous nalbuphine-based regimens for attenuation of postoperative pruritus and related side effects in combination with epidural morphine patient-controlled analgesia with regard to the quality of postoperative pain management. Patients were randomly assigned to two nalbuphine groups (5 μg/kg/hour, Group N5 or 10 μg/kg/hour, Group N10) and bolus dose of 1.6 μg/kg for PCP or the control (normal saline) group. Comparable visual analog scale scores for rest pain at each measured time interval among the three groups demonstrated that adequate pain relief was offered; however, the cumulative dose of nalbuphine administered to the patients in Group N10 attenuated the analgesic effect of epidural morphine in moving pain at POh24 only. Fewer episodes and milder severity of pruritus were observed in patients in Groups N5 and N10 at all postoperative time intervals. Epidural morphine provided good postoperative pain relief but with incommodious side effects. In addition, intravenous nalbuphine not only attenuated the incidence of pruritus but also decreased total morphine consumption. In conclusion, intravenous administration of low-dose nalbuphine (5 μg/kg/hour) for PCP maintained analgesia produced by epidural morphine and offered low pruritus incidence.
- Olea Europea-derived phenolic products attenuate antinociceptive morphine tolerance: an innovative strategic approach to treat cancer pain. [Journal Article]
- J Biol Regul Homeost Agents 2014 Jan-Mar; 28(1):105-16.
Morphine and related opioid drugs are currently the major drugs for severe pain. Their clinical utility is limited in the management of severe cancer pain due to the rapid development of tolerance. Restoring opioid efficacy is therefore of great clinical importance. A great body of evidence suggests the key role of free radicals and posttranslational modulation in the development of tolerance to the analgesic activity of morphine. Epidemiological studies have shown a relationship between the Mediterranean diet and a reduced incidence of pathologies such as coronary heart disease and cancer. A central hallmark of this diet is the high consumption of virgin olive oil as the main source of fat which contains antioxidant components in the non-saponifiable fraction, including phenolic compounds absent in seed oils. Here, we show that in a rodent model of opiate tolerance, removal of the free radicals with phenolic compounds of olive oil such as hydroxytyrosol and oleuropein re-instates the analgesic action of morphine. Chronic injection of morphine in mice led to the development of tolerance and this was associated with increased nitrotyrosin and malondialdehyde (MDA) formation together with nitration and deactivation of MnSOD in the spinal cord. Removal of free radicals by hydroxytyrosol and oleuropein blocked morphine tolerance by inhibiting nitration and MDA formation and replacing the MnSOD activity. The phenolic fraction of virgin olive oil exerts antioxidant activities in vivo and free radicals generation occurring during chronic morphine administration play a crucial role in the development of opioid tolerance. Our data suggest novel therapeutic approach in the management of chronic cancer pain, in particular for those patients who require long-term opioid treatment for pain relief without development of tolerance.
- The alpha3beta4* nicotinic acetylcholine receptor subtype mediates physical dependence to morphine: mouse and human studies. [JOURNAL ARTICLE]
- Br J Pharmacol 2014 Apr 21.
Recent data have indicated that α3β4* neuronal nicotinic acetylcholine receptors (nAChRs) may play a role in morphine dependence. Here we investigated if nAChRs modulate morphine physical withdrawal.To assess the role of α3β4* neuronal nicotinic acetylcholine receptors in morphine withdrawal, we used a genetic correlation approach using publically available data sets within the GeneNetwork web resource, genetic knockout and pharmacological tools. Lastly, male and female European-American (n=2,772) and African-American (n=1,309) subjects from the SAGE dataset were used to assess the possible association of polymorphisms in the 15q25 gene cluster and opioid dependence.BXD recombinant mouse lines demonstrated an increase in expression of α3, β4, and α5 nAChR mRNA in the forebrain and midbrain, which significantly correlates with an increase in defecation in mice undergoing morphine withdrawal. Indeed, mice with overexpression of the gene cluster CHRNA5/A3/B4 exhibited an increase in somatic signs of withdrawal. Furthermore, α5 and β4 nAChR knockout mice expressed decreased somatic withdrawal signs compared to their wildtype counterparts. Moreover, selective α3β4* nAChR antagonists, α-conotoxin AuIB (AuIB) and AT-1001, attenuated somatic signs of morphine withdrawal in a dose-related manner. In addition, two human datasets revealed a protective role for variants in the CHRNA3 gene, which codes for the α3 nAChR subunit, in opioid dependence and withdrawal. In contrast, we found that the α4β2* nAChR subtype is not involved in morphine somatic withdrawal signs.Overall, our findings suggest an important role for the α3β4* nAChR subtype in morphine physical dependence.
- Management of the acute painful crisis in sickle cell disease- a re-evaluation of the use of opioids in adult patients. [JOURNAL ARTICLE]
- Br J Haematol 2014 Apr 18.
Management of the acute painful crisis (APC) of sickle cell disease (SCD) remains unsatisfactory despite advances in the understanding and management of acute pain in other clinical settings. One reason for this is an unsophisticated approach to the use of opioid analgesics for pain management. This applies to haematologists who are responsible for developing acute sickle pain management protocols for their patients, and to health care staff in the acute care setting. The objective of this article is to evaluate the evidence for use of opioids in APC management. We have highlighted the possibilities for improving management by using alternatives to morphine, and intranasal (IN) or transmucosal routes of administration for rapid onset of analgesia in the emergency department (ED). We suggest how experience gained in managing acute sickle pain in children could be extrapolated to adolescents and young adults. We have also questioned whether patients given strong opioids in the acute setting are being safely monitored and what resources are required to ensure efficacy, safety and patient satisfaction. We also identify aspects of care where there are significant differences of opinion, which require further study by randomized controlled trial.
- Postoperative morphine concentration in infants with or without biliary atresia and its association with hepatic blood flow. [JOURNAL ARTICLE]
- Anaesthesia 2014 Apr 18.
We measured pre-operative hepatic blood flow and postoperative morphine concentration in infants with or without biliary atresia. Thirty-four infants (0-3 months) with biliary atresia undergoing portoenterostomy (Kasai operation) were included and hepatic blood flow was assessed by magnetic resonance imaging before surgery in 12 of them. Sixteen subjects (0-3 months) without liver disease undergoing abdominal or pelvic surgery acted as controls and six of them had hepatic blood flow assessed. Intravenous morphine (8 μg.kg(-1) .h(-1) ) was administered to all patients postoperatively. The median (IQR [range]) relative hepatic blood flow was 3.51 (2.72-3.88 [1.68-4.43]) with and 3.15 (2.66-4.42 [2.30-5.01]) without biliary atresia (p = 0.851). The median (IQR [range]) morphine concentration after 24 h infusion was 5.9 (4.5-16.4 [2.9-42.2]) ng.ml(-1) and 6.4 (3.2-12.0 [1.9-48.6]) ng.ml(-1) , respectively (p = 0.460). An inverse regression relation was found between the morphine concentration and the hepatic perfusion index (R(2) = 0.519, p = 0.001). Compensatory increases in hepatic arterial blood flow maintain the total hepatic blood flow in infants with biliary atresia.