A comprehensive review of sedative and analgesic agents

Transforming growth factor-beta proteins are key regulators of cellular growth and differentiation. To understand the role of TGF-beta in colonic tumour progression, 47 paraffin embedded samples from colonic tumours (13 adenomas, and 34 adenocarcinomas) were studied. Gene mutations in the region coding for the active protein were studied by PCR SSCP analysis of exons 5, 6, and 7. TGF-beta1 mRNA expression and localization were studied by NISH using cDNA probes generated by RT-PCR. Protein distribution was investigated by immunohistochemistry using antibodies against both intracellular and extracellular forms. Three mutations were found: one in exon 5 (Dukes C) and two in exon 7 (Dukes C and A). TGF-beta1 mRNA was observed in 9 (69%) of 13 adenomas and in 30 (88%) of 34 adenocarcinomas. Levels of TGF-beta1 mRNA and proteins were higher in colorectal carcinomas than in colorectal adenomas. Tubular adenomas associated with dysplasia showed greater expression of TGF-beta1 than adenomas without dysplasia and than non-neoplastic colonic mucosa. In dysplasia and cancer, epithelial neoplastic cells and stromal cells were positive for TGF-beta1. In normal tissue endothelial cells and granulocytes sporadically showed immunoreactivity for TGF-beta1, whereas epithelial cells were all negative. The three mutations in TGF-beta1 exons 5, 6 and 7 found in colorectal adenocarcinomas suggest that TGF-beta1 mutation may play a role in colorectal carcinogenesis and that the presence of the mutant form contributes to the transformed state. Our two other findings, the loss of staining gradient in normal colonic mucosa and the higher levels of TGF-beta1 mRNA and proteins in colorectal carcinomas than in colorectal adenomas, indicate that the de-regulation of TGF-beta1 expression may occur as an early event in colorectal carcinogenesis. Although TGF-beta1 expression is generally a reflection of cellular differentiation, tumour grade is not associated with TGF-beta1 mRNA expression. Beside being present in the epithelial cells of the colonic tumours, TGF-beta1 mRNA also occurred in the stroma: its localization in the macrophages adjacent to tumour strongly suggests that TGF-beta1 could be secreted by macrophages. This hypothesis should lead to new therapeutic strategies for colorectal carcinoma.     

The effect of music and lyrics on personality.

An experiment tested whether music can produce significant changes in the experience of one's own personality traits under laboratory conditions. Participants were 87 first-year undergraduates at a large Canadian university (58 women and 29 men; mean age = 18.3 years). After completing a set of questionnaires including the Big Five Inventory, they were divided into 3 groups: the music-and-lyrics group listened to a classical song while reading the English translation of lyrics, the music-only group listened to a classical song and followed along the text of lyrics in German, and the lyrics-only group listened to the English translation of the lyrics, while following its text as well. Participants were then readministered the Big Five Inventory within another set of questionnaires. The results show that music produced significant increases, and lyrics significant decreases, in the short-term self-reported experience of change of one's personality traits. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

The effect of constant baroque music on premature infants

A rapid and simple method for the in vitro evaluation of the virulence of F. tularensis is proposed. The optimal parameters--the concentrations of bacteria and the substrate (phenolphthalein phosphate), the time incubation in the serum--have been developed and special conditions for strains of different subspecies have been selected. The proposed method makes it possible to greatly reduce the time of obtaining results and to exclude labor-consuming experiments on laboratory animals when working with large collections of F. tularensis laboratory and natural wild strains. Moreover, the method widens the possibilities of experimenters in the evaluation of the effect of some mutation on the virulence of the strain under study.     

Acute withdrawal syndrome related to the administration of analgesic and sedative medications in adult intensive care unit patients

OBJECTIVES: To estimate the frequency of acute withdrawal syndrome related to the administration of analgesic and sedative medications in mechanically ventilated adult intensive care unit (ICU) patients; to identify associated clinical factors. DESIGN: Retrospective review of medical records. SETTING: An adult trauma/surgical ICU in an urban Level I trauma center. PATIENTS: Twenty-eight mechanically ventilated adult trauma/ surgical ICU patients requiring >7 days of ICU care. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Daily doses of all opioid, sedative, hypnotic, and major tranquilizer drugs administered to each patient were measured, as was duration of ICU stay, duration of mechanical ventilation, and duration of the administration of analgesic, sedative, and neuromuscular blocking agents (NMBAs) for each patient. All opioids and benzodiazepines were converted to their respective fentanyl and lorazepam equivalent units based on potency and bioavailability. Calculation of the weaning rate for each patient during tapering from opioid and benzodiazepine medications was performed. The presence or absence of acute withdrawal syndrome was identified for each patient. Nine (32.1%) patients developed acute withdrawal syndrome potentially related to the administration of analgesic or sedative medications. Patients in the withdrawal group received significantly higher mean daily (p = .049) and peak (p = .032) doses of fentanyl equivalents, as well as higher mean daily lorazepam equivalents (p = .049) compared with patients not experiencing withdrawal. Patients in the withdrawal group were also significantly more likely to have received neuromuscular blocking agents (p = .004) or propofol (p =.026) for >1 day during ICU admission compared with patients not experiencing withdrawal. Duration of mechanical ventilation (p = .049), benzodiazepine therapy (p = .048), and propofol therapy (p = .049) was also significantly longer in the group experiencing withdrawal. Withdrawal patients received a significantly lower mean daily dose of haloperidol (p = .026). There was a significant association between the development of withdrawal syndrome and the presence of ARDS (p = .017). Finally, the slopes of the lines representing opioid and benzodiazepine drug weaning were more steep for the withdrawal group, although these results did not achieve statistical significance. CONCLUSIONS: These results suggest that mechanically ventilated adult patients with extended ICU care (> or =7 days) who receive large doses of analgesic and sedative medications are at risk for acute withdrawal syndromes during drug weaning. The association between ARDS and withdrawal syndrome, combined with the observation that withdrawal syndromes were also associated with the use of neuromuscular blocking agents and prolonged mechanical ventilation, suggests that patients with ARDS may be more likely to receive high doses of analgesic and sedative medications, and are therefore at increased risk for withdrawal syndrome.     

The analgesic effect of PCA buprenorphine in Taiwan''s gynecologic patients

Bloodless cardiac surgery would be optimal for all patients undergoing major or complex heart surgery; however, for Jehovah's Witnesses it involves a religious law and is fundamentally mandated. In this context, we review a case of unstable angina with associated anemia requiring catheterization and definitive intervention in a Jehovah's Witness patient. Coronary stenting to stabilize the acute coronary syndrome is described with definitive total revascularization performed by coronary artery bypass graft surgery after utilizing erythropoietin and aggressive blood conservation techniques.     

Cortical potentials evoked by tooth pulp stimulation differentiate between the analgesic and sedative effects of morphine in awake rats

This study was undertaken to determine whether the cortical potential (CEP) evoked by noxious electrical stimulation of the incisor tooth pulp can be used to measure analgesia in the presence of sedation in the awake rat. Changes in the CEP produced by morphine (5, 10 and 20 mg/kg s.c.), an opioid analgesic with sedative effects, were compared with those produced by droperidol (1.25 mg/kg s.c.), a neuroleptic agent with no analgesic activity. Both drugs had similar small effects on CEP latency. However, whereas morphine produced a dose-related decrease in amplitude and area under the curve, particularly in the earliest component of the CEP, droperidol produced an increase in amplitude and area under the curve. Naloxone (0.5-2 mg/kg s.c.) reversed all effects of morphine. Similar CEPs could be evoked by electrical stimulation of the tooth pulp or surrounding gingiva in lightly anesthetized rats. However, the tooth pulp stimulation-evoked CEP was unchanged after anesthesia of the gingiva with lidocaine, and the gingiva-evoked CEP was unchanged after anesthesia of the tooth pulp. Therefore, stimulation of the rat's incisor can selectively activate intrapulpal fibers, which are sufficient to generate a CEP. This CEP is an indicator of nociception which can be used to distinguish the analgesic effects of drugs such as morphine from their sedative effects.     

Comparison of sedative and analgesic/anesthetic effects induced by medetomidine, acepromazine, azaperone, droperidol and midazolam in laboratory pigs

The sedative and analgesic/anesthetic effects of medetomidine, acepromazine, azaperone, droperidol and midazolam were compared in laboratory pigs. In these sedatives, medetomidine produced the most profound degree of sedation with greater drowsiness than was achieved by other sedatives tested. Medetomidine induced sedation accompanied with weak analgesia and muscle relaxation smoothly and quickly and depressed arousal reaction deeply as compared with other sedatives. Pigs given medetomidine were not aroused easily even by moderately rough stimulation for approximately 60 min after injection.     

臭氧联合镇痛液治疗膝关节滑膜炎疗效观察

目的 观察臭氧联合镇痛液关节腔内注射治疗膝关节滑膜炎临床疗效.方法 选取360例膝关节滑膜炎患者,随机分为治疗组和对照组,180例/组.治疗组给予臭氧联合镇痛液关节腔注射治疗;对照组仅给予关节腔内注射镇痛液.对比观察两组患者治疗后的效果.结果 治疗组优130例,良45例、差5例,对照组优90例,良60例,差30例,治疗组优良率(97.2%)显著高于对照组(83.3%),差异具有统计学意义(P<0.05).结论 臭氧联合镇痛液关节腔内注射治疗膝关节临床疗效优于单纯镇痛液关节腔内注射.     

Is all sparing created equal? Comparing lag-1 sparing and extended sparing in temporal object perception.

When two targets (T1, T2) are presented amongst a rapid stream of distractors, T2 accuracy is impaired if the targets are separated by at least one distractor (attentional blink). However, this impairment largely disappears if the targets follow one another directly (lag-1 sparing), and, in fact, as many as four or five consecutive targets may be identified quite accurately under these conditions (extended sparing). Although all current models propose a common mechanism for both lag-1 and extended sparing, this hypothesis has yet to be tested. To this end, we examined the effect of various types of attentional switches, known to impact lag-1 sparing, on extended sparing in order to determine whether they would have a similar effect. Results suggested substantial parallels between the two types of sparing. We discuss these results in terms of a unified account of sparing in temporal object perception. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Corticosteroid sparing effect of low dose methotrexate treatment in adult Still''s disease

The techniques of molecular imprinting and sensitized lanthanide luminescence have been combined to create the basis for a sensor that can selectively measure the hydrolysis product of the nerve agent Soman in water. The sensor functions by selectively and reversibly binding the phosphonate hydrolysis product of this agent to a functionality-imprinted copolymer possessing a coordinatively bound luminescent lanthanide ion, Eu3+. Instrumental support for this device is designed to monitor the appearance of a narrow luminescence band in the 610-nm region of the Eu3+ spectrum that results when the analyte is coordinated to the copolymer. The ligand field shifted luminescence was excited using 1 mW of the 465.8-nm line of an argon ion laser and monitored via an optical fiber using a miniature spectrometer. For this configuration, the limit of detection for the hydrolysis product is 7 parts per trillion (ppt) in solution with a linear range from 10 ppt to 10 ppm. Chemical and spectroscopic selectivities have been combined to reduce the likelihood of false positive analyses. Chemically analogous organophosphorus pesticides tested against the sensor have been shown to not interfere with determination.     

Relationship between pharmacokinetics and the analgesic effect of ketorolac in the rat

The relationship between the pharmacokinetic properties and the analgesic effect of ketorolac was evaluated with the pain-induced functional impairment model in the rat. Female Wistar rats were injected with uric acid in the knee of the right hind limb to produce dysfunction. Then, animals received an oral dose of 0.3, 1, 1.8, 3.2 or 5.6 mg/kg of ketorolac tromethamine and analgesic effect and blood concentration, determined by high-performance liquid chromatography, were evaluated at selected times for a period of 4 hr. Ketorolac produced a dose-dependent analgesic effect, measured as a recovery of the functionality of the injured limb, which reached its maximal effect at doses of 3.2 mg/kg or higher. When functionality index was plotted against ketorolac blood concentration, a direct relationship was observed that was well described by the sigmoidal maximal effect model. The data strongly suggest that ketorolac's analgesic effect depends on the blood concentration of the drug.     

Loss of analgesic effect of morphine due to coadministration of rifampin

The nature of weak selection differs between coding and non-coding regions. Coding regions contain genetic information, whereas most non-coding regions do not have any information. Genetic information may be regarded as interaction systems, and the NK model of Kauffman was analysed. This model assumes that each amino acid makes a fitness contribution that depends on the amino acid and on K other amino acids among the N that make the protein. Through simulations, it was found that there are numerous nearly-neutral mutations under this model. Therefore, evolution is rapid in small populations, and slow in large populations. The variance of the evolutionary rate is not quite as large as data indicate under the model, and additional factors, such as environmental change or population-size fluctuation, need to be considered. Weak selection at non-coding regions may come from chromosome organization, and may be regional in character, which differs from that at coding regions. The problem of genetic load is thought to disappear in these circumstances.     

The effect of item position on the likelihood of identification by inference in prose reading and music reading.

In experiments with 21 university students (Exp I) and 7 adult musicians (Exp II), Ss were presented with verbal and musical texts which contained spelling and notational errors, respectively. Measures of detection in normal unpaced reading situations showed that errors were least likely to be detected when they occurred in the middle of words or musical phrases, demonstrating that the highest proportion of inferences occurred at these positions. The apparent similarities of the effects in music and language reading suggest that inference of interior elements usually results from structural rather than visual factors. (French summary) (28 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effect of tourniquet release time on the analgesic efficacy of intraarticular morphine after arthroscopic knee surgery

A randomized, controlled study was conducted in patients undergoing elective arthroscopic knee surgery to assess the effects of tourniquet release time on analgesia after intraarticular (I.A.) injection of morphine. Standardized general anesthetic and surgical techniques were used for all patients, including a thigh tourniquet inflated at pressures between 300 and 350 mm Hg. At the conclusion of the arthroscopic procedure, 5 mg morphine in 25 mL saline was administered I.A. Patients were then randomized to one of two treatment groups. In Group 1 (n = 20), the tourniquet was kept inflated for 10 min after I.A. injection, whereas in Group 2 (n = 20), the tourniquet was deflated immediately after I.A. injection. Postoperative pain was assessed using a visual analog scale in the recovery room when the patients were awake and at 2, 4, 6, 8, and 24 h after I.A. injection. Patients who complained of pain in the recovery room received increments of intravenous meperidine 25-50 mg. On discharge from the recovery room, patients received oral mefenamic acid 250-500 mg for pain relief. The time and quantity of analgesics required were recorded. Patients in Group 1 had significantly (P < 0.05) lower pain scores than those in Group 2 at 2, 4, 6, and 8 h postoperatively. These low pain scores were associated with lower requirements of supplementary analgesics. We conclude that, as compared with releasing the tourniquet immediately after I.A. injection of morphine, maintaining the tourniquet inflated for 10 min provides superior analgesia and decreases the need for supplemental analgesics.     

Identification of the receptor subtype involved in the analgesic effect of neurotensin

The neuropeptide neurotensin (NT) elicits hypothermic and naloxone-insensitive analgesic responses after brain injection. Recent pharmacological evidence obtained with NT agonists and antagonists suggests that these effects are mediated by a receptor distinct from the initially cloned high-affinity NT receptor (NTR1). The recent cloning of a second NT receptor (NTR2) prompted us to evaluate its role in NT-induced analgesia. Intracerebroventricular injections in mice of two different antisense oligodeoxynucleotides from the NTR2 markedly decreased NTR2 mRNA and protein and reduced NT-induced analgesia. This effect was specific, because NTR1 levels were unaffected, and sense or scramble oligodeoxynucleotides had no effect. Structure-activity studies revealed a close correlation between the analgesic potency of NT analogs and their affinity for the NTR2 and disclosed potent and selective agonists of this receptor. These data confirm that NTR1 is involved in the NT-elicited turning behavior and demonstrate that the NTR2 mediates NT-induced analgesia.