[Therapeutic effect of the latest extracorporal elimination procedure (Prometheus treatment) in acute liver failure caused by intoxication]

Orv Hetil. 2007 Oct 21;148(42):1981-8

Authors: Bakos A, Rikker C, Tóvárosi S, Kárteszi M

INTRODUCTION: Despite intensive therapy the mortality of acute liver failure without organ transplantation is 60-90%. Because of organ shortage in liver transplantation, a significant number of patients dies while being on the waiting list. In order to diminish the mortality, various trials were introduced to remove the albumin-bound and water-soluble toxins in liver failure with the aim to support the spontaneous regeneration of the liver and maintaining the patients alive until liver transplantation. Prometheus treatment is a relatively new technique combining Fractionated Plasma Separation and Adsorption (FPSA) with a high-flux dialysis. During the procedure the patient's own separated albumin-rich plasma passes through special adsorbents making possible the elimination of albumin-bound toxins, while hemodialysis gets rid of water-soluble toxins. AIM: The authors' intention was to demonstrate the efficiency of Prometheus treatment in acute liver failure caused by intoxication. PATIENTS AND METHOD: Prometheus treatment was indicated in three patients who suffered from severe intoxication with paracetamol, potassium permanganate and Amanita phalloides, which resulted in a hepatic failure incurable with conservative therapy. RESULTS: Ten treatments were performed in the three female patients. No serious complication was observed. Due to the treatment the albumin-bound (indirect bilirubin p = 0.048; bile acid p = 0.001) and water-soluble (direct bilirubin p = 0.002; creatinine p = 0.007) toxins were significantly decreased. The level of ammonia, urea nitrogen, fibrinogen and antithrombin III did not change significantly. All the three patients were cured without liver transplantation. CONCLUSION: Prometheus treatment removes efficiently the accumulating toxins in acute liver failure. It is a safe elimination technique. In cases untreatable with conservative therapy it makes possible maintaining the patients alive until the liver regenerates spontaneously, or liver transplantation is feasible.

PMID: 17932004 [PubMed - indexed for MEDLINE]

Effects of Ganoderma lucidum polysaccharide on CYP2E1, CYP1A2 and CYP3A activities in BCG-immune hepatic injury in rats.

Biol Pharm Bull. 2007 Sep;30(9):1702-6

Authors: Wang X, Zhao X, Li D, Lou YQ, Lin ZB, Zhang GL

The purpose of the present study was to investigate the effect of Ganoderma lucidum polysaccharide (GLPS), a major active component in Chinese medicinal fungus, on cytochrome P450 metabolic activity in Bacillus Calmette Guérin (BCG)-induced immune hepatic injury in rats. The enzyme kinetics of the probes including chlorzoxazone (CYP2E1), phenacetin (CYP1A2) and nifedipine (CYP3A) were evaluated by HPLC. The results showed that BCG-pretreatment (125 mg/kg) significantly increased serum levels of alanine transaminase (ALT), nitrite and malondialdehyde (MDA), inhibited activities of superoxide dismutase (SOD) and decreased P450 total content in microsomes (p<0.05). Administration of GLPS (50 and 200 mg/kg) reversed above hepatic injury stimulated by BCG in vivo. Moreover, GLPS dose-dependently inhibited activities of CYP2E1, CYP1A2 and CYP3A in hepatic microsomes in vitro, suggesting that inhibition of GLPS on P450 oxidative metabolism might participate in the hepatoprotective mechanism, and also suggested that pharmacokinetics might be changed by drug-herb interaction.

PMID: 17827724 [PubMed - indexed for MEDLINE]

Evaluation of human hepatocyte chimeric mice as a model for toxicological investigation using panomic approaches--effect of acetaminophen on the expression profiles of proteins and endogenous metabolites in liver, plasma and urine.

J Toxicol Sci. 2007 Aug;32(3):205-15

Authors: Yamamoto T, Tomizawa K, Fujikawa M, Sato Y, Yamada H, Horii I

Toxicological responses to acetaminophen (APAP) overdose were evaluated in human hepatocytes transplanted chimeric mice using 2-dimensional gel electrophoresis (2DE)-based proteomics and (1)H-nuclear magnetic resonance (NMR)-based metabonomics. Huge variations, which were supported by histopathological findings, were observed in proteins expression in chimeric mice liver. The proteomic analysis of the livers showed that the proteins involved in the pathways of lipid/fatty acid metabolism, glycolysis and energy metabolism/production were affected. In addition, oxidative stress-related proteins showed altered expression. The metabonomic analysis of urine and plasma revealed alterations of endogenous metabolites, which were the intermediates involved in the tricarboxylic acid (TCA) cycle. Those findings were already confirmed in normal mice. We hypothesized that the mechanism of APAP-induced effects on chimeric mice liver was in accordance with the mechanism observed in normal mice. Therefore, these toxicopanomic approaches successfully revealed that the mechanisms in humans were identical with "known" APAP-induced hepatotoxicity detected in chimeric mice. Further investigations are needed to detect idiosyncratic hepatotoxicity in humans using chimeric mice.

PMID: 17785938 [PubMed - indexed for MEDLINE]

Acetaminophen overdose and N-acetylcysteine therapy.

Ann Acad Med Singapore. 2007 Aug;36(8):704

Authors: Chong VH

PMID: 17767345 [PubMed - indexed for MEDLINE]

Transdermal delivery of hydrophobic and hydrophilic local anesthetics from o/w and w/o Brij 97-based microemulsions.

J Pharm Pharm Sci. 2007;10(3):288-98

Authors: Junyaprasert VB, Boonme P, Songkro S, Krauel K, Rades T

PURPOSE: To characterize the physicochemical properties of drug-loaded oil-in-water (o/w) and water-in-oil (w/o) Brij 97-based microemulsions in comparison to their blank counterparts and to investigate the influence of microemulsion type on in vitro skin permeation of model hydrophobic drugs and their hydrophilic salts. METHODS: The microemulsion systems were composed of isopropyl palmitate (IPP), water and a 2:1 w/w mixture of Brij 97 and 1-butanol. The samples were characterized by visual appearance, pH, refractive index, electrical conductivity, viscosity and determination of the state of water and IPP in the formulations using differential scanning calorimetry (DSC). Transdermal flux of lidocaine, tetracaine, dibucaine and their respective hydrochloride salts through heat-separated human epidermis was investigated in vitro using modified Franz diffusion cells. RESULTS: The physicochemical properties of drug-loaded microemulsions and their blank counterparts were generally similar; however, slight changes in some physicochemical properties (apparent pH and conductivity) were observed due to the intrinsic properties of the drugs. The o/w microemulsions resulted in the highest flux of lidocaine, tetracaine and dibucaine as compared to the other formulations with in the same group of drugs. CONCLUSIONS: The characterization results showed that incorporation of the model drugs into the microemulsions did not change the microemulsion type. The permeation data exhibited that the nature of the microemulsions was a crucial parameter for transdermal drug delivery. The o/w microemulsions containing hydrophobic drugs provided the highest skin permeation enhancement. In addition, skin permeation was depended on the molecular weight of the model drugs.

PMID: 17727792 [PubMed - indexed for MEDLINE]

Butachlor-induced acute toxic hepatitis.

Indian J Gastroenterol. 2007 May-Jun;26(3):135-6

Authors: Daryani NE, Hosseini P, Bashashati M, Haidarali M, Sayyah A

Butachlor is a highly effective herbicidal substance widely used by farmers. We report a 60-year-old man with exfoliative dermatitis, jaundice, increase in liver enzymes and eosinophilia one day after accidental dermal exposure to butachlor toxin. The diagnostic workup showed no other cause and liver histology was consistent with substance-induced toxic hepatitis. Within two weeks of conservative therapy, his liver function tests returned to normal.

PMID: 17704582 [PubMed - indexed for MEDLINE]

Increased anion gap metabolic acidosis as a result of 5-oxoproline (pyroglutamic acid): a role for acetaminophen.

Clin J Am Soc Nephrol. 2006 May;1(3):441-7

Authors: Fenves AZ, Kirkpatrick HM, Patel VV, Sweetman L, Emmett M

The endogenous organic acid metabolic acidoses that occur commonly in adults include lactic acidosis; ketoacidosis; acidosis that results from the ingestion of toxic substances such as methanol, ethylene glycol, or paraldehyde; and a component of the acidosis of kidney failure. Another rare but underdiagnosed cause of severe, high anion gap metabolic acidosis in adults is that due to accumulation of 5-oxoproline (pyroglutamic acid). Reported are four patients with this syndrome, and reviewed are 18 adult patients who were reported previously in the literature. Twenty-one patients had major exposure to acetaminophen (one only acute exposure). Eighteen (82%) of the 22 patients were women. Most of the patients were malnourished as a result of multiple medical comorbidities, and most had some degree of kidney dysfunction or overt failure. The chronic ingestion of acetaminophen, especially by malnourished women, may generate high anion gap metabolic acidosis. This undoubtedly is an underdiagnosed condition because measurements of serum and/or urinary 5-oxoproline levels are not readily available.

PMID: 17699243 [PubMed - indexed for MEDLINE]

Montelukast in 2 atopic patients with intolerance to nonsteroidal anti-inflammatory drugs and paracetamol: 5-year follow-up.

J Investig Allergol Clin Immunol. 2007;17(4):278-9

Authors: Morais-Almeida M, Marinho S, Gaspar A

PMID: 17694705 [PubMed - indexed for MEDLINE]

ICVTS on-line discussion A. The safety of using millimolar doses of lidocaine as cardioplegia.

Interact Cardiovasc Thorac Surg. 2007 Apr;6(2):176

Authors: Fallouh HB, Chambers DJ

PMID: 17669803 [PubMed - indexed for MEDLINE]

Lidocaine-magnesium blood cardioplegia was equivalent to potassium blood cardioplegia in left ventricular function of canine heart.

Interact Cardiovasc Thorac Surg. 2007 Apr;6(2):172-6

Authors: Yamaguchi S, Watanabe G, Tomita S, Tabata S

This study evaluated the effects of lidocaine-magnesium blood cardioplegia on left ventricular function compared with potassium blood cardioplegia. Crystalloid cardioplegia which contains lidocaine has been reported but blood cardioplegia is rare. Thirteen dogs received 60 min of global ischemia under hypothermic cardioplumonary bypass (30 degrees C). Potassium blood cardioplegia was administered every 20 min in group A (n=6), and lidocaine-magnesium blood cardioplegia in group B (n=7). We compared the ratio of Emax obtained during IVC occlusion at pre- and post-global ischemia (%Emax) and LVSW (%LVSV). Cardiac function was evaluated prior to CPB and 60 min after reperfusion. There was no difference in time required for cardiac arrest between the two groups (group A: 78+/-3 s, group B: 89+/-9 s). Percentage maximal elastance was significantly better in group B (group A: 63+/-3%, group B: 76+/-4%, P<0.05). Percentage tissue water content of the myocardium after CPB was significantly lower in group B (group A: 82.3+/-4%, group B: 75.5+/-2%, P<0.05). Lidocaine-magnesium blood cardioplegia was equivalent to potassium blood cardioplegia in systolic left ventricular function and reduced myocardial edema in canine heart.

PMID: 17669802 [PubMed - indexed for MEDLINE]

Fluoroscopically guided caudal epidural steroid injections in degenerative lumbar spine stenosis.

Pain Physician. 2007 Jul;10(4):547-58

Authors: Botwin K, Brown LA, Fishman M, Rao S

BACKGROUND: Caudal epidural steroid injections are commonly utilized to help reduce radicular pain in lumbar spinal stenosis. There have been studies done to evaluate the effectiveness of this procedure non-fluoroscopically guided. Search revealed no prospective studies evaluating the effectiveness of fluoroscopically guided caudal epidural injections on patients with bilateral radicular pain from degenerative lumbar spinal stenosis. OBJECTIVE: To evaluate the therapeutic benefit of fluoroscopically guided caudal epidural steroid injections in the treatment of bilateral radicular pain from symptomatic Degenerative Lumbar Spinal Stenosis (DLSS). DESIGN: This prospective cohort study was performed on 34 patients with bilateral radicular pain from lumbar spinal stenosis who received fluoroscopically guided caudal epidural injections at a multidisciplinary spine center as they did not improve with conservative care. The patients' degenerative lumbar spinal stenosis was confirmed by magnetic resonance imaging and classified as mild, moderate, or severe. The patients were evaluated by an independent observer and completed questionnaires, prior to initial injection, at 6 weeks, 6 months and 12 months after the injections. OUTCOME MEASURES: Visual analog scale, patient satisfaction scale, standing/walking tolerance scale and Oswestry low back pain disability questionnaire. RESULTS: A total of 34 patients met our inclusion criteria and were followed at 6 weeks, 6 months, and 12 months. Sixty-five percent of patients at 6 weeks, 62% at 6 months, and 54% at 12 months had a successful outcome, reporting at least a >50% reduction between pre-injection and post injection visual analog pain scores. Fifty nine percent of patients had an improved walking tolerance at 6 weeks (p <0.0001), 56% at 6 months (p <0.0001), and 51% at 12 months (p=0.0005). Fifty percent of patients had an improved standing tolerance at 6 weeks (p= 0.0002), 54% at 6 months (p < 0.0001), and 51% at 12 months (p=0.0005). The patient satisfaction scale revealed 64% of patients felt completely or somewhat better at 6 weeks, 59% at 6 months and 52% at 12 months. Owestry low back pain disability questionnaire scores showed statistically significant improvement from initial scores to 6 weeks (p < 0.0001), initial to 6 months (p= 0.0095), and initial to 12 months (p=0.00015). The outcome was statistically significant even in severe stenotic patients when comparing initial mean scores to 12 month mean scores in standing tolerance (p =0.2956), walking tolerance (p=0.0250), and VAS (p= 0.0199). CONCLUSION: Fluoroscopically guided caudal epidural steroid injections may help reduce bilateral radicular pain and improve standing and walking tolerance in patients with DLSS.

PMID: 17660853 [PubMed - indexed for MEDLINE]

Effect of intraocular surgery and ketamine on aqueous and serum cytokines.

Mol Vis. 2007;13:1130-7

Authors: Tu KL, Kaye SB, Sidaras G, Taylor W, Shenkin A

PURPOSE: To determine the effect of intraocular surgery and anesthesia on aqueous and serum cytokines. METHODS: Patients undergoing routine cataract surgery under general and local (peribulbar) anesthesia were randomized to those given general anesthetic with and without the use of ketamine and those having local anesthesia. Aqueous and serum levels of cytokines were collected at commencement of surgery and were determined by an immunoassay using multi-analyte biochip array technology at 18 h post-operatively. RESULTS: At 18 h postoperative, all patients (37) showed significant and many fold increases in their aqueous levels of interleukin (IL)-1alpha, IL-1beta, IL-4, IL-6, IL-8, vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, epidermal growth factor (EGF), and monocyte chemotactic protein (MCP)-1. There was little to no increase in IL-2 and IL-10. Significant increases in some cytokines (EGF, IL-6, and IFN-gamma) in the serum were also found (p=0.038). There were no significant differences in aqueous cytokine levels following the use of ketamine or between those patients who had general and local anesthesia (0.11<p<0.97). CONCLUSIONS: There is an aqueous and serum cytokine response following intraocular surgery whether local (peribulbar) or general anesthesia is used. Of the aqueous cytokines measured, three different patterns of responses emerged at 18 h post-cataract surgery; those that were highly increased (IL-8, IL-6, IFN-gamma, and TNF-alpha), medium increase (IL-1beta, VEGF, IL-4, and MCP-1), and those with little to no change (EGF, IL-1alpha, IL-2, and IL-10).

PMID: 17653058 [PubMed - indexed for MEDLINE]

Emergency department visits for acetaminophen overdose: a Canadian population-based epidemiologic study (1997-2002).

CJEM. 2007 Jul;9(4):267-74

Authors: Myers RP, Li B, Shaheen AA

OBJECTIVE: We describe the epidemiology of emergency department (ED) visits for acetaminophen overdose in a large Canadian health region, with a focus on sociodemographic risk factors and temporal trends. METHODS: Patients presenting to an ED in the Calgary Health Region (population approximately 1.1 million) for acetaminophen overdose between 1997 and 2002 were identified using regional administrative data. RESULTS: A total of 2699 patients made 3015 ED visits for acetaminophen overdose between 1997 and 2002, corresponding to an age- and sex-adjusted incidence of 45.7 per 100,000 population. Alcohol-related disorders were common (19%) and overdose rates were higher in females, younger patients, Aboriginals and social assistance recipients. The incidence decreased from 52.6 per 100,000 in 1997 to 35.1 per 100,000 in 2002 (34% relative reduction; p < 0.0005). When classified according to suicidal intent, the rates of intentional and unintentional overdose (69% and 25% of all overdoses, respectively) showed similar temporal trends. A marked seasonality was observed, with a peak in spring and early summer. CONCLUSIONS: ED visit rates for acetaminophen overdose fell between 1997 and 2002. High-risk groups, including young females and marginalized populations, may benefit from preventive and educational initiatives.

PMID: 17626691 [PubMed - indexed for MEDLINE]

Hospitalizations for acetaminophen overdose: a Canadian population-based study from 1995 to 2004.

BMC Public Health. 2007;7:143

Authors: Myers RP, Li B, Fong A, Shaheen AA, Quan H

BACKGROUND: Acetaminophen overdose (AO) is the most common cause of acute liver failure. We examined temporal trends and sociodemographic risk factors for AO in a large Canadian health region. METHODS: 1,543 patients hospitalized for AO in the Calgary Health Region (population ~1.1 million) between 1995 and 2004 were identified using administrative data. RESULTS: The age/sex-adjusted hospitalization rate decreased by 41% from 19.6 per 100,000 population in 1995 to 12.1 per 100,000 in 2004 (P < 0.0005). This decline was greater in females than males (46% vs. 29%). Whereas rates fell 46% in individuals under 50 years, a 50% increase was seen in those >/= 50 years. Hospitalization rates for intentional overdoses fell from 16.6 per 100,000 in 1995 to 8.6 per 100,000 in 2004 (2004 vs. 1995: rate ratio [RR] 0.49; P < 0.0005). Accidental overdoses decreased between 1995 and 2002, but increased to above baseline levels by 2004 (2004 vs. 1995: RR 1.24;P < 0.0005). Risk factors for AO included female sex (RR 2.19; P < 0.0005), Aboriginal status (RR 4.04; P < 0.0005), and receipt of social assistance (RR 5.15; P < 0.0005). CONCLUSION: Hospitalization rates for AO, particularly intentional ingestions, have fallen in our Canadian health region between 1995 and 2004. Young patients, especially females, Aboriginals, and recipients of social assistance, are at highest risk.

PMID: 17615056 [PubMed - indexed for MEDLINE]

Bulleyaconitine A isolated from aconitum plant displays long-acting local anesthetic properties in vitro and in vivo.

Anesthesiology. 2007 Jul;107(1):82-90

Authors: Wang CF, Gerner P, Wang SY, Wang GK

BACKGROUND: Bulleyaconitine A (BLA) is an active ingredient of Aconitum bulleyanum plants. BLA has been approved for the treatment of chronic pain and rheumatoid arthritis in China, but its underlying mechanism remains unclear. METHODS: The authors examined (1) the effects of BLA on neuronal voltage-gated Na channels in vitro under the whole cell patch clamp configuration and (2) the sensory and motor functions of rat sciatic nerve after single BLA injections in vivo. RESULTS: BLA at 10 microm did not affect neuronal Na currents in clonal GH3 cells when stimulated infrequently to +50 mV. When stimulated at 2 Hz for 1,000 pulses (+50 mV for 4 ms), BLA reduced the peak Na currents by more than 90%. This use-dependent reduction of Na currents by BLA reversed little after washing. Single injections of BLA (0.2 ml at 0.375 mm) into the rat sciatic notch not only blocked sensory and motor functions of the sciatic nerve but also induced hyperexcitability, followed by sedation, arrhythmia, and respiratory distress. When BLA at 0.375 mm was coinjected with 2% lidocaine (approximately 80 mm) or epinephrine (1:100,000) to reduce drug absorption by the bloodstream, the sensory and motor functions of the sciatic nerve remained fully blocked for approximately 4 h and regressed completely after approximately 7 h, with minimal systemic effects. CONCLUSIONS: BLA reduces neuronal Na currents strongly at +50 mV in a use-dependent manner. When coinjected with lidocaine or epinephrine, BLA elicits prolonged block of both motor and sensory functions in rats with minimal adverse effects.

PMID: 17585219 [PubMed - indexed for MEDLINE]

Erythema multiforme to tetrazepam.

J Investig Allergol Clin Immunol. 2007;17(3):205-6

Authors: Cabrerizo Ballesteros S, M&#xE9;ndez Alcalde JD, Sánchez Alonso A

PMID: 17583114 [PubMed - indexed for MEDLINE]

Warnings for makers of compounded pain products.

FDA Consum. 2007 Mar-Apr;41(2):20-2

Authors: Meadows M

PMID: 17582862 [PubMed - indexed for MEDLINE]

Cardiovascular alterations after injection of 2% lidocaine with norepinephrine 1:50,000 (xylestesin) in rats.

Anesth Prog. 2007;54(2):45-9

Authors: Faraco FN, Armonia PL, Malamed SF

The purpose of the present study is to determine the cardiovascular effects produced by intravascular injection of 2% lidocaine with 20 microg/mL of norepinephrine on systolic, diastolic, and mean arterial pressures and heart rate of rats at the following times: control period, during the injection (first 15 seconds), during the first minute, and at the end of 1, 2, 3, 4, 5, 10, 15, 20, 25, and 30 minutes after drug administration. The study was performed on 13 male Wistar rats with weights between 200 grams and 220 grams that were awake during the recording of these parameters. The dose administered was proportional to 1 cartridge of local anesthetic (1.8 mL) in an average-size human, which is equivalent to 0.51 mg/kg of lidocaine hydrochloride and 0.51 microg/kg of norepinephrine hydrochloride. The average time of injection was 15.7 seconds. The results of this study showed significant increases in systolic, diastolic, and mean arterial pressure and a noticeable decrease in heart rate. The greatest variation occurred in the systolic blood pressure. The greatest alterations occurred during injection and within the first minute following administration of the anesthetic solution. We would anticipate these changes in the parameters analyzed to be clinically significant. Thus, dentists using 2% lidocaine with norepinephrine 20 mug/mL should be very careful to avoid intravascular injection.

PMID: 17579502 [PubMed - indexed for MEDLINE]

Comparison of 1.5% lidocaine and 0.5% ropivacaine epidural anesthesia combined with propofol general anesthesia guided by bispectral index.

J Zhejiang Univ Sci B. 2007 Jun;8(6):428-34

Authors: Xiang Y, Li YH

OBJECTIVE: To compare the effects of epidural anesthesia with 1.5% lidocaine and 0.5% ropivacaine on propofol requirements, the time to loss of consciousness (LOC), effect-site propofol concentrations, and the hemodynamic variables during induction of general anesthesia guided by bispectral index (BIS) were studied. METHODS: Forty-five patients were divided into three groups to receive epidurally administered saline (Group S), 1.5% (w/w) lidocaine (Group L), or 0.5% (w/w) ropivacaine (Group R). Propofol infusion was started to produce blood concentration of 4 mug/ml. Once the BIS value reached 40~50, endotracheal intubation was facilitated by 0.1 mg/kg vecuronium. Measurements included the time to LOC, effect-site propofol concentrations, total propofol dose, mean arterial blood pressure (MABP), and heart rate (HR) at different study time points. RESULTS: During induction of anesthesia, both Groups L and R were similar for the time to LOC, effect-site propofol concentrations, total propofol dose, MABP, HR, and BIS. The total doses of propofol administered until 1 min post-intubation were significantly less in patients of Groups R and L compared with Group S. MABP and HR were significantly lower following propofol induction compared with baseline values in the three groups, or MABP was significantly increased following intubation as compared with that prior to intubation in Group S but not in Groups R and L while HR was significantly increased following intubation in the three groups. CONCLUSION: Epidural anesthesia with 1.5% lidocaine and 0.5% ropivacaine has similar effects on the time to LOC, effect-site propofol concentrations, total propofol dose, and the hemodynamic variables during induction of general anesthesia.

PMID: 17565514 [PubMed - indexed for MEDLINE]

Levator ani syndrome - a case study and literature review.

Aust Fam Physician. 2007 Jun;36(6):449-52

Authors: Ng CL

BACKGROUND: Although anorectal symptoms are a common problem seen in general practice, general practitioners may sometimes encounter patients presenting with anorectal pain without a detectable cause. OBJECTIVE: This article discusses a case of recurrent anorectal pain in a young woman due to levator ani syndrome, and the current evidence for treatment of levator ani syndrome. DISCUSSION: Levator ani syndrome usually presents with recurrent or chronic rectal pain without detectable organic pathology. Digital massage, sitz bath, muscle relaxants, electrogalvanic stimulation and biofeedback are the treatment modalities most frequently described in the literature.

PMID: 17565405 [PubMed - indexed for MEDLINE]

Prospective analysis on the relation between pain and prostate volume during transrectal prostate biopsy.

Korean J Radiol. 2007 May-Jun;8(3):231-5

Authors: Yun TJ, Lee HJ, Kim SH, Lee SE, Byun SS, Hong SK, Cho JY, Seong CK

OBJECTIVE: We wanted to assess the relationship between pain and the prostate volume during transrectal ultrasound (TRUS) guided biopsy. MATERIALS AND METHODS: Between July and September 2006, 71 patients scheduled for TRUS biopsy of the prostate were considered for inclusion to this study. These patients underwent periprostatic neurovascular bundle block with lidocaine prior to biopsy. Pain was assessed using a Visual Analogue Scale (VAS) during periprostatic neurovascular bundle block (VAS 1), during biopsy (VAS 2), and 20 minutes after biopsy (VAS 3). The mean pain scores were analyzed in the large prostate group (prostate volume > 40 cc) and the small prostate group (prostate volume< or =40 cc). P values < 0.05 were considered significant. RESULTS: The mean prostate volume was 42.2 cc (standard deviation: 8.6). The mean pain scores of VAS 1, 2 and 3 were 4.70+/-1.61, 3.15+/-2.44 and 1.05+/-1.51, respectively. In the large prostate group, the mean pains scores of VAS 1, 2 and 3 were 4.75+/-1.76, 3.51+/-2.76 and 1.29+/-1.70, respectively, whereas in the small prostate group, the means pain scores were 4.66+/-1.46, 2.77+/-2.0, and 0.80+/-1.26, respectively. Although there were no statistical differences of VAS 1, the larger prostate group revealed higher pain scores of VAS 2 and 3 compared with the small prostate group (p < 0.05). CONCLUSION: Patients with larger prostate volumes tend to feel more pain during and after TRUS guided prostate biopsy. Our findings suggest that additional analgesic strategies may be necessary when the patients with larger prostate undergo TRUS guided prostate biopsy.

PMID: 17554191 [PubMed - indexed for MEDLINE]

The effect of acetaminophen (four grams a day for three consecutive days) on hepatic tests in alcoholic patients--a multicenter randomized study.

BMC Med. 2007;5:13

Authors: Kuffner EK, Green JL, Bogdan GM, Knox PC, Palmer RB, Heard K, Slattery JT, Dart RC

BACKGROUND: Hepatic failure has been associated with reported therapeutic use of acetaminophen by alcoholic patients. The highest risk period for alcoholic patients is immediately after discontinuation of alcohol intake. This period exhibits the largest increase in CYP2E1 induction and lowest glutathione levels. Our hypothesis was that common liver tests would be unaffected by administration of the maximum recommended daily dosage of acetaminophen for 3 consecutive days to newly-abstinent alcoholic subjects. METHODS: Adult alcoholic subjects entering two alcohol detoxification centers were enrolled in a prospective double-blind, randomized, placebo-controlled trial. Subjects were randomized to acetaminophen, 4 g/day, or placebo for 3 consecutive days. The study had 95% probability of detecting a 15 IU/L difference in serum ALT. RESULTS: A total of 443 subjects were enrolled: 308 (258 completed) received acetaminophen and 135 subjects (114 completed) received placebo. Study groups did not differ in demographics, alcohol consumption, nutritional status or baseline laboratory assessments. The peak mean ALT activity was 57 +/- 45 IU/L and 55 +/- 48 IU/L in the acetaminophen and placebo groups, respectively. Subgroup analyses for subjects presenting with an elevated ALT, subjects fulfilling a diagnosis of alcoholic hepatitis and subjects attaining a peak ALT greater than 200 IU/L showed no statistical difference between the acetaminophen and control groups. The one participant developing an increased international normalized ratio was in the placebo group. CONCLUSION: Alcoholic patients treated with the maximum recommended daily dose of acetaminophen for 3 consecutive days did not develop increases in serum transaminase or other measures of liver injury. Treatment of pain or fever for 3 days with acetaminophen appears safe in newly-abstinent alcoholic patients, such as those presenting for acute medical care.

PMID: 17537264 [PubMed - indexed for MEDLINE]

Acute pain in adults admitted to the emergency room: development and implementation of abbreviated guidelines.

Swiss Med Wkly. 2007 Apr 21;137(15-16):223-7

Authors: Tamch&#xE8;s E, Buclin T, Hugli O, Decosterd I, Blanc C, Moushine E, Givel JC, Yersin B

AIM: Although acute pain is frequently reported by patients admitted to the emergency room, it is often insufficiently evaluated by physicians and is thus undertreated. With the aim of improving the care of adult patients with acute pain, we developed and implemented abbreviated clinical practice guidelines (CG) for the staff of nurses and physicians in our hospital's emergency room. METHODS: Our algorithm is based upon the practices described in the international literature and uses a simultaneous approach of treating acute pain in a rapid and efficacious manner along with diagnostic and therapeutic procedures. RESULTS: Pain was assessed using either a visual analogue scale (VAS) or a numerical rating scale (NRS) at ER admission and again during the hospital stay. Patients were treated with paracetamol and/or NSAID (VAS/NRS <4) or intravenous morphine (VAS/NRS > or =04). The algorithm also outlines a specific approach for patients with headaches to minimise the risks inherent to a non-specific treatment. In addition, our algorithm addresses the treatment of paroxysmal pain in patients with chronic pain as well as acute pain in drug addicts. It also outlines measures for pain prevention prior to minor diagnostic or therapeutic procedures. CONCLUSIONS: Based on published guidelines, an abbreviated clinical algorithm (AA) was developed and its simple format permitted a widespread implementation. In contrast to international guidelines, our algorithm favours giving nursing staff responsibility for decision making aspects of pain assessment and treatment in emergency room patients.

PMID: 17525877 [PubMed - indexed for MEDLINE]

Topical lidocaine and epidural bupivacaine/hydromorphone in the treatment of complex regional pain syndrome type 2.

Pain Physician. 2007 May;10(3):513-4

Authors: Vorobeychik Y, Giampetro DM

PMID: 17525787 [PubMed - indexed for MEDLINE]

Hydrocodone use and sensorineural hearing loss.

Pain Physician. 2007 May;10(3):467-72

Authors: Ho T, Vrabec JT, Burton AW

BACKGROUND: The hydrocodone/acetaminophen combination is one of the most commonly used analgesic preparations. Isolated incidences of suspected association between hydrocodone abuse and rapidly progressive hearing loss have been reported. In this study, we describe the clinical characteristics of 5 patients presenting with progressive hearing loss and a history of hydrocodone use. METHODS: Patients presenting with rapidly progressive bilateral hearing loss who had a documented history of hydrocodone use were selected for the study. The presentation, audiologic findings, associated comorbidities, and treatment outcomes were reviewed. RESULTS: All patients displayed rapidly progressive sensorineural hearing loss without vestibular symptoms. Hearing loss was asymmetric in 3 patients at initial presentation, but progressed to profound loss, usually within months. Steroid treatment has no effect on the progression of the hearing loss. The admitted quantity of hydrocodone consumed ranged from 10 to 300 mg per day. Hepatitis C was the most common comorbidity, present in 60% of the patients. All patients underwent cochlear implantation with satisfactory results. CONCLUSIONS: The chronic use of hydrocodone can be associated with progressive sensorineural hearing loss. Successful auditory rehabilitation can be achieved with cochlear implantation. Genetic polymorphisms of drug metabolizing enzymes as well as associated comorbidities such as hepatitis C infection may be significant in the development of hydrocodone ototoxicity, though additional investigations are necessary.

PMID: 17525781 [PubMed - indexed for MEDLINE]

Successful introduction of modified dorsolumbar epidural anesthesia in a bovine referral center.

J Vet Sci. 2007 Jun;8(2):181-4

Authors: Hiraoka M, Miyagawa T, Kobayashi H, Takahashi T, Kishi H, Kobayashi H, Lee I

This study describes the successful use of modified dorsolumbar epidural anesthesia with a fixed volume of anesthetic in a bovine referral center. Among the 130 Holstein cattle scheduled for flank surgery, 90 cattle received a mixed anesthetic consisting of 1 ml of xylazine hydrochloride and 3 ml of lidocaine hydrochloride by modified dorsolumbar epidural anesthesia. Eighteen cattle with dehydration and/or lameness received a mixed anesthetic containing 0.5 ml of xylazine and 3 ml of lidocaine. Infiltration anesthesia was performed in 22 cattle whose epidural space could not be reached in order to perform the flank surgery. The surgeries began about 12 min after the administration of the anesthetic and lasted for about 36 min. The modified method using a fixed volume of anesthetic was successfully introduced and effectively used in a bovine referral center. This modified method will allow veterinarians to save time and effort, thus lowering the cost of each surgery.

PMID: 17519573 [PubMed - indexed for MEDLINE]

Anesthetic effects of lidocaine hydrochloride gel using low frequency ultrasound of 0.5 MHz.

J Pharm Pharm Sci. 2007;10(1):1-8

Authors: Kim TY, Jung DI, Kim YI, Yang JH, Shin SC

PURPOSE: Low-frequency ultrasound has a significant effect on the transdermal permeation of high molecular weight drugs. However, the rate of permeation in pulsed mode is quite low necessitating considerable time to apply the ultrasound. 0.5 MHz ultrasound, which is a relatively higher frequency in the low-frequency range, can be applied in high intensity in continuous mode. METHODS: A transducer was used to administer an anesthetic drug transdermally on healthy volunteers. The anesthetic effect was measured following administration on placebo, lidocaine HCl alone and lidocaine HCl with 0.5 and 1.0 MHz ultrasound (n=8/group). RESULTS: In surface anesthesia, the phonophoresis group showed a significantly higher pain threshold than the other groups but there was no significant difference between the phonophoresis groups according to the ultrasound frequency. In conduction anesthesia, the 0.5 MHz phonophoresis group showed a significant change in their pain threshold and amplitude of sensory nerve action potential (SNAP) compared with the other groups. CONCLUSIONS: Although there are limitations in applying 0.5 MHz ultrasound in phonophoresis for conduction anesthesia using lidocaine hydrochloride for a nerve block, it is more effective than the 1 Mhz that is widely used in clinical situations.Carbamazepine is a poor water soluble drug and its bioavailability is limited by dissolution rate. Dissolution, serum concentration and anticonvulsive effect of the drug have been evaluated after cogrinding with microcrystalline cellulose. A cogrinding technique was used to increase the dissolution, serum concentrations and anticonvulsive effect of the drug. A novel deconvolution technique of in vitro-in vivo correlation was evaluated.

PMID: 17498388 [PubMed - indexed for MEDLINE]

Protein targets of reactive electrophiles in human liver microsomes.

Chem Res Toxicol. 2007 Jun;20(6):859-67

Authors: Shin NY, Liu Q, Stamer SL, Liebler DC

Liver microsomes are widely used to study xenobiotic metabolism in vitro, and covalent binding to microsomal proteins serves as a surrogate marker for toxicity mediated by reactive metabolites. We have applied liquid chromatography-tandem mass spectrometry (LC-MS-MS) to identify protein targets of the biotin-tagged model electrophiles 1-biotinamido-4-(4'-[maleimidoethylcyclohexane]-carboxamido)butane (BMCC) and N-iodoacetyl-N-biotinylhexylenediamine (IAB) in human liver microsomes. The biotin-tagged peptides resulting from in-gel tryptic digestion were enriched by biotin-avidin chromatography and LC-MS-MS was used to identify 376 microsomal cysteine thiol targets of BMCC and IAB in 263 proteins. Protein adduction was selective and reproducible, and only 90 specific cysteine sites in 70 proteins (approximately 25% of the total) were adducted by both electrophiles. Differences in adduction selectivity correlated with different biological effects of the compounds, as IAB- but not BMCC-induced ER stress in HEK293 cells. Targeted LC-MS-MS analysis of microsomal glutathione-S-transferase cysteine 50, a target of both IAB and BMCC, detected time-dependent adduction by the reactive acetaminophen metabolite N-acetyl-p-benzoquinoneimine during microsomal incubations. The results indicate that electrophiles selectively adduct microsomal proteins, but display differing target selectivities that correlate with differences in toxicity. Analysis of selected microsomal protein adduction reactions thus could provide a more specific indication of potential toxicity than bulk covalent binding of radiolabeled compounds.

PMID: 17480101 [PubMed - indexed for MEDLINE]

Minocycline-induced acute eosinophilic pneumonia: controversial results of lymphocyte stimulation test and re-challenge test.

Intern Med. 2007;46(9):593-5

Authors: Ono E, Miyazaki E, Matsuno O, Nureki S, Okubo T, Ando M, Kumamoto T

We report an instructive case of minocycline-induced eosinophilic pneumonia confirmed by re-challenge test, in which a preceding lymphocyte-stimulation test indicated acetaminophen as the etiologic agent. A 55-year-old woman developed high fever and lung infiltrates with pulmonary eosinophilia after exposure to minocycline, acetaminophen, theophylline and procaterol. All of the medicines were discontinued, resulting in prompt improvement. The lymphocyte stimulation tests provided a positive result for acetaminophen, but not for the other medicines; however, a negative result was given by a re-challenge test with acetaminophen. In contrast, symptoms and hypoxemia reappeared when minocycline was re-administered. We would like to emphasize that lymphocyte stimulation test results need to be carefully interpreted for individual drugs.

PMID: 17473496 [PubMed - indexed for MEDLINE]

Molecular complex consisting of two typical external medicines: intermolecular interaction between indomethacin and lidocaine.

Chem Pharm Bull (Tokyo). 2007 May;55(5):832-6

Authors: Umeda Y, Fukami T, Furuishi T, Suzuki T, Makimura M, Tomono K

The molecular complex formed between indomethacin (IDM) and lidocaine (LDC), which are typical external medicines, was studied. A thermal analysis, microscopic study and phase solubility technique suggested intermolecular interaction between IDM and LDC. The phase solubility profiles with IDM and LDC were classified as A(L)-type, indicating the formation of a 1 : 1 stoichiometric molecular complex. The apparent stability constant (K(S)), calculated from the slope and the intercept, was 4478.9 M(-1). A molecular ion peak was detected at 592.2 (m/z) from fast-atom bombardment-MS measurements, which was in accordance with the sum of the molecular weight for IDM (M(W): 357.81) and LDC (M(W): 234.38). The changes of IR spectra in the C=O stretching region showed that each intact hydrogen bond network was collapsed in the IDM-LDC system and strong interaction between IDM and LDC formed after their kneading. From the (1)H-NMR analyses, it was estimated that the dominant interactive site was the IDM carboxylic acid group which associated with the LDC diethyl amino group non-covalently.

PMID: 17473482 [PubMed - indexed for MEDLINE]

Drug-induced lymphocyte stimulation test is not useful for the diagnosis of drug-induced pneumonia.

Tohoku J Exp Med. 2007 May;212(1):49-53

Authors: Matsuno O, Okubo T, Hiroshige S, Takenaka R, Ono E, Ueno T, Nureki S, Ando M, Miyazaki E, Kumamoto T

Diagnosis of drug-induced pneumonia, which represents pulmonary toxicity caused by certain drugs, is difficult, as a large number of different drugs can elicit various immune-mediated diseases with distinct pathomechanisms. The drug-induced lymphocyte stimulation test (DLST) is widely used for diagnosing drug-induced pneumonia in Japan. Recent reports, however, indicate that DLST is not reliable for diagnosis of drug-induced pneumonia. To diagnose drug-induced pneumonia, a provocation test with the suspected drug is the most reliable method of assessing the relationship between the drug and pneumonia. We examined the correlation between the DLST and the provocation test in 6 cases of suspected drug-induced pneumonia. DLST was performed in all of the patients. The causes of pneumonia in all patients were confirmed by a provocation test. The DLST was positive in 3 of 6 cases of suspected drug-induced pneumonia, but the suspected drugs were ruled out by the provocation test. If we had relied solely on the DLST, these 3 cases would have been labeled as false allergy. The results of the DLST did not coincide with the results of the provocation test in any of the cases. Our results suggest that the DLST is not useful for the diagnosis of drug-induced pneumonia. Following provocation with the causative drug, reappearance of pulmonary infiltration was not observed in any of the cases. These findings indicate that a carefully performed provocation test is the safe and most reliable method.

PMID: 17464103 [PubMed - indexed for MEDLINE]

Factors associated with allergic rhinitis in children from northern Mexico City.

J Investig Allergol Clin Immunol. 2007;17(2):77-84

Authors: Del-R&#xED;o-Navarro BE, Luna-Pech JA, Berber A, Zepeda-Ortega B, Avila-Castañon L, Del-Río-Chivardi JM, Baeza-Bacab M, Sienra-Monge JJ

BACKGROUND: The International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire allows users to find factors associated with allergic diseases, but thus far most of the studies on risk factors for allergic diseases have been devoted to asthma and not to rhinitis. OBJECTIVE: To determine the main factors associated with symptoms of allergic rhinitis and rhinoconjunctivitis in school children and adolescents in northern Mexico City. PATIENTS AND METHODS: A cross sectional, multicenter survey was conducted in northern Mexico City, in children aged 6-7 and 13-14 years. The survey instrument was the Phase Three B ISAAC questionnaire, which was validated and standardized in Spanish. RESULTS: There were 4106 6-7-year-olds and 6576 13-14-year-olds. The total prevalence of diagnosis of allergic rhinitis was 4.6%. The prevalence of cumulative and current symptoms of rhinitis was considered high (>29%), but the prevalence of the diagnosis of allergic rhinitis was considered low (ranging from 3.4% to 5.6%). The prevalence of symptoms of rhinitis with conjunctivitis had intermediate values (ranging from 20.3% to 30.2%). Cumulative symptoms of allergic rhinitis, current symptoms of allergic rhinitis, and rhinoconjunctivitis were related to symptoms of current or cumulative asthma, symptoms of current or cumulative atopic eczema, and current use of paracetamol (odds ratio > 1, P < .05). CONCLUSION: The present results support the concept of rhinitis and asthma as common chronic respiratory diseases, and this study also found a relation between paracetamol use and rhinitis in children.

PMID: 17460945 [PubMed - indexed for MEDLINE]

Effects of ranolazine on recurrent cardiovascular events in patients with non-ST-elevation acute coronary syndromes: the MERLIN-TIMI 36 randomized trial.

JAMA. 2007 Apr 25;297(16):1775-83

Authors: Morrow DA, Scirica BM, Karwatowska-Prokopczuk E, Murphy SA, Budaj A, Varshavsky S, Wolff AA, Skene A, McCabe CH, Braunwald E,

CONTEXT: Ranolazine is a novel antianginal agent that reduces ischemia in patients with chronic angina but has not been studied in patients with acute coronary syndromes (ACS). OBJECTIVE: To determine the efficacy and safety of ranolazine during long-term treatment of patients with non-ST-elevation ACS. DESIGN, SETTING, AND PATIENTS: A randomized, double-blind, placebo-controlled, multinational clinical trial of 6560 patients within 48 hours of ischemic symptoms who were treated with ranolazine (initiated intravenously and followed by oral ranolazine extended-release 1000 mg twice daily, n = 3279) or matching placebo (n = 3281), and followed up for a median of 348 days in the Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndromes (MERLIN)-TIMI 36 trial between October 8, 2004, and February 14, 2007. MAIN OUTCOME MEASURES: The primary efficacy end point was a composite of cardiovascular death, myocardial infarction (MI), or recurrent ischemia through the end of study. The major safety end points were death from any cause and symptomatic documented arrhythmia. RESULTS: The primary end point occurred in 696 patients (21.8%) in the ranolazine group and 753 patients (23.5%) in the placebo group (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.83-1.02; P = .11). The major secondary end point (cardiovascular death, MI, or severe recurrent ischemia) occurred in 602 patients (18.7%) in the ranolazine group and 625 (19.2%) in the placebo group (HR, 0.96; 95% CI, 0.86-1.08; P = .50). Cardiovascular death or MI occurred in 338 patients (10.4%) allocated to ranolazine and 343 patients (10.5%) allocated to placebo (HR, 0.99; 95% CI, 0.85-1.15; P = .87). Recurrent ischemia was reduced in the ranolazine group (430 [13.9%]) compared with the placebo group (494 [16.1%]; HR, 0.87; 95% CI, 0.76-0.99; P = .03). QTc prolongation requiring a reduction in the dose of intravenous drug occurred in 31 patients (0.9%) receiving ranolazine compared with 10 patients (0.3%) receiving placebo. Symptomatic documented arrhythmias did not differ between the ranolazine (99 [3.0%]) and placebo (102 [3.1%]) groups (P = .84). No difference in total mortality was observed with ranolazine compared with placebo (172 vs 175; HR, 0.99; 95% CI, 0.80-1.22; P = .91). CONCLUSIONS: The addition of ranolazine to standard treatment for ACS was not effective in reducing major cardiovascular events. Ranolazine did not adversely affect the risk of all-cause death or symptomatic documented arrhythmia. Our findings provide support for the safety and efficacy of ranolazine as antianginal therapy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00099788.

PMID: 17456819 [PubMed - indexed for MEDLINE]

Percutaneous penetration kinetics of lidocaine and prilocaine in two local anesthetic formulations assessed by in vivo microdialysis in pigs.

Biol Pharm Bull. 2007 Apr;30(4):830-4

Authors: Wei H, Chen Y, Xu L, Zheng J

The aim of this study was to characterize and compare the percutaneous penetration kinetics of lidocaine (L) and prilocaine (P) in two local anesthetic formulations by in vivo microdialysis coupled with HPLC. The microdialysis system for studying lidocaine and prilocaine was calibrated by a no-net-flux method in vitro and retrodialysis method in vivo, respectively. A dosage of 0.2 g/cm2 of an in-house P-L formulation (2.5% lidocaine and 2.5% prilocaine, methylcellulose-based) and commercially available Eutectic Mixture of Local Anesthesia (EMLA, 2.5% lidocaine and 2.5% prilocaine, carbopol-based) was separately but symmetrically applied in the dorsal region of pigs. Saline (0.9%, w/v) was perfused into the linear microdialysis probe at a flow rate of 1.5 microl/min. Dialysate was collected upon topical application up to 6 h at 20-min intervals and assessed by HPLC. The results demonstrated the area under the concentration-time curve (AUC(0-6 h)) of lidocaine and prilocaine in EMLA was 71.95+/-23.36 microg h/ml and 38.01+/-14.8 microg h/ml, respectively, in comparison to 167.11+/-56.12 microg h/ml and 87.02+/-30.38 microg h/ml in the P-L formulation. The maximal concentrations (Cmax) of lidocaine and prilocaine in the dermis were 29.2+/-9.08 microg/ml and 16.54+/-5.31 microg/ml in EMLA and 80.93+/-17.98 microg/ml and 43.69+/-12.87 microg/ml in the P-L formulation, respectively. This study indicates a well-calibrated microdialysis system can provide vital real-time information on percutaneous drug delivery and specifically a methylcellulose-based P-L formulation can increase percutaneous absorption of both lidocaine and prilocaine in pigs compared to carbopol-based EMLA.

PMID: 17409532 [PubMed - indexed for MEDLINE]

Accidental paracetamol poisoning.

Med J Aust. 2007 Apr 2;186(7):371-2

Authors: Lubel JS, Angus PW, Gow PJ

PMID: 17407437 [PubMed - indexed for MEDLINE]

Does restricting pack size of paracetamol (acetaminophen) reduce suicides?

PLoS Med. 2007 Apr;4(4):e152

Authors: Buckley NA, Gunnell D

PMID: 17407389 [PubMed - indexed for MEDLINE]

Interrupted time-series analysis of regulations to reduce paracetamol (acetaminophen) poisoning.

PLoS Med. 2007 Apr;4(4):e105

Authors: Morgan OW, Griffiths C, Majeed A

BACKGROUND: Paracetamol (acetaminophen) poisoning is the leading cause of acute liver failure in Great Britain and the United States. Successful interventions to reduced harm from paracetamol poisoning are needed. To achieve this, the government of the United Kingdom introduced legislation in 1998 limiting the pack size of paracetamol sold in shops. Several studies have reported recent decreases in fatal poisonings involving paracetamol. We use interrupted time-series analysis to evaluate whether the recent fall in the number of paracetamol deaths is different to trends in fatal poisoning involving aspirin, paracetamol compounds, antidepressants, or nondrug poisoning suicide. METHODS AND FINDINGS: We calculated directly age-standardised mortality rates for paracetamol poisoning in England and Wales from 1993 to 2004. We used an ordinary least-squares regression model divided into pre- and postintervention segments at 1999. The model included a term for autocorrelation within the time series. We tested for changes in the level and slope between the pre- and postintervention segments. To assess whether observed changes in the time series were unique to paracetamol, we compared against poisoning deaths involving compound paracetamol (not covered by the regulations), aspirin, antidepressants, and nonpoisoning suicide deaths. We did this comparison by calculating a ratio of each comparison series with paracetamol and applying a segmented regression model to the ratios. No change in the ratio level or slope indicated no difference compared to the control series. There were about 2,200 deaths involving paracetamol. The age-standardised mortality rate rose from 8.1 per million in 1993 to 8.8 per million in 1997, subsequently falling to about 5.3 per million in 2004. After the regulations were introduced, deaths dropped by 2.69 per million (p = 0.003). Trends in the age-standardised mortality rate for paracetamol compounds, aspirin, and antidepressants were broadly similar to paracetamol, increasing until 1997 and then declining. Nondrug poisoning suicide also declined during the study period, but was highest in 1993. The segmented regression models showed that the age-standardised mortality rate for compound paracetamol dropped less after the regulations (p = 0.012) but declined more rapidly afterward (p = 0.031). However, age-standardised rates for aspirin and antidepressants fell in a similar way to paracetamol after the regulations. Nondrug poisoning suicide declined at a similar rate to paracetamol after the regulations were introduced. CONCLUSIONS: Introduction of regulations to limit availability of paracetamol coincided with a decrease in paracetamol-poisoning mortality. However, fatal poisoning involving aspirin, antidepressants, and to a lesser degree, paracetamol compounds, also showed similar trends. This raises the question whether the decline in paracetamol deaths was due to the regulations or was part of a wider trend in decreasing drug-poisoning mortality. We found little evidence to support the hypothesis that the 1998 regulations limiting pack size resulted in a greater reduction in poisoning deaths involving paracetamol than occurred for other drugs or nondrug poisoning suicide.

PMID: 17407385 [PubMed - indexed for MEDLINE]

A comparison of the lidocaine patch 5% vs naproxen 500 mg twice daily for the relief of pain associated with carpal tunnel syndrome: a 6-week, randomized, parallel-group study.

MedGenMed. 2006;8(3):33

Authors: Nalamachu S, Crockett RS, Gammaitoni AR, Gould EM

OBJECTIVES: Carpal tunnel syndrome (CTS) is a common entrapment neuropathy caused by median nerve compression. This pilot clinical trial was designed to compare the safety and effectiveness of the lidocaine patch 5% to that of naproxen 500 mg twice daily for the treatment of neuropathic pain associated with CTS. METHODS: In this 6-week, randomized, parallel-group, open-label, multicenter study, participants from 2 practice sites, aged 18 to 75 years with clinical/electrodiagnostic evidence of CTS, were randomized to receive up to 3 lidocaine 5% patches every 24 hours or naproxen 500 mg twice daily for 6 weeks. Outcome assessments included mean changes between baseline and Week 6 average pain intensity (Brief Pain Inventory [BPI]: Question 5, Average Pain Intensity [API]), an Investigator Clinical Global Impression of Improvement (CGI-I) over the course of the treatment period and a comparison of patient satisfaction (Clinical Global Assessment of Treatment [CGAT]). RESULTS: One hundred patients were randomized in this study, 52 in the lidocaine patch 5% group and 48 in the naproxen 500 mg twice daily group. Significant reductions in API scores were observed between baseline and Week 6 for both lidocaine patch 5% (P < .0001) and naproxen 500 mg twice daily (P = .0004); however, there were no statistically significant differences between treatments (P = .083). There was a significant (P = .016) difference in the CGI-I for lidocaine patch 5% (51.1%) compared with naproxen 500 mg twice daily (24.3%). Whereas 71.8% of the lidocaine patch 5% patients reported being "satisfied" to "very satisfied" with the treatment, only 63.2% of naproxen 500 mg twice daily patients reported likewise, although the difference was not statistically significant. Both treatments were well tolerated. Two patients reported treatment-related adverse events in the lidocaine patch 5% group and 6 in the naproxen 500 mg twice daily group, all of which were considered mild or moderate in severity. CONCLUSIONS: This study demonstrates that the lidocaine patch 5% is effective in significantly relieving the pain associated with CTS and is well tolerated. The patch may offer patients an effective, nonsystemic, noninvasive treatment for the management of their symptoms. Further controlled studies are warranted.

PMID: 17406167 [PubMed - indexed for MEDLINE]

Safety of cataract surgery under topical anesthesia with oral sedation without anesthetic monitoring.

Can J Ophthalmol. 2007 Apr;42(2):288-94

Authors: Rocha G, Turner C

PURPOSE: The current study was conducted to determine whether topical anesthesia with oral sedation and without an anesthetist present in the operating room is a safe and cost-effective strategy for low-risk patients undergoing cataract surgery. METHODS: This retrospective interventional case series included cases conducted between 2001 and 2003 at the Brandon Regional Health Centre in Brandon, Manitoba. Patients with visually significant cataracts were screened for study inclusion by using the following criteria: good general health, good dilation, moderate cataracts, cooperation with in-office tests and procedures, and understanding of cataract surgery. Oral sedation was provided by lorazepam, and an anesthetist was available to manage any medical adverse events. Topical anesthesia was achieved by means of tetracaine drops, lidocaine hydrochloride jelly, and intracameral lidocaine hydrochloride, as necessary. Main outcome measures were heart rate, systolic and diastolic blood pressure, oxygen saturation, intraoperative complications, and medical adverse events necessitating anesthetist intervention. RESULTS: A total of 538 eyes of 373 patients were included in the cataract surgery case series. No medical adverse events were reported in 454 cases (84.4%); 84 patients (15.6%) experienced adverse events, classified as mild in 13.5%, moderate in 1.1%, and severe in 0.9% (5 cases). The most common adverse event was mild pain, experienced in 69 procedures (12.8%). Moderate pain, necessitating use of intracameral 1% lidocaine, occurred in 3 procedures (0.6%). INTERPRETATION: Topical anesthesia appears to be a safe alternative to injection anesthesia without many of the disadvantages of the latter and may be preferable in carefully selected patients.

PMID: 17392854 [PubMed - indexed for MEDLINE]

Case series on chronic whiplash related neck pain treated with intraarticular zygapophysial joint regeneration injection therapy.

Pain Physician. 2007 Mar;10(2):313-8

Authors: Hooper RA, Frizzell JB, Faris P

BACKGROUND: Although in clinical use, there is only 1 published case report on the efficacy of intraarticular regeneration injection therapy (RIT) (a.k.a. prolotheraphy). This report supports a rationale for future clinical trials of this technique. OBJECTIVE: To assess the efficacy of intraarticular zygapophysial joint RIT in patients with chronic whiplash related neck pain that failed other conservative and interventional procedures. Patients were treated with intraarticular RIT and reassessed over 1 year. DESIGN: Retrospective case review of prospective data. MATERIALS and METHODS: Eighteen consecutive patients were treated with intraarticular prolotherapy by placing 0.5 - 1mL of 20% dextrose solution into each zygapophysial joint, after confirmation of intraarticular location with radiographic contrast, using 25-gauge spinal needles and fluoroscopic guidance. Solution was prepared by diluting D50W with 1% lidocaine. RESULTS: Fifteen patients completed treatment. Three patients had bilateral treatment, leaving 18 sides for analysis. Mean Neck Disability Index (NDI) pre-treatment was 24.71 and decreased post-treatment to 14.21 (2 months), 13.45 (6 months), 10.94 (12 months). Average change NDI=13.77 (p<0.0001) baseline versus 12 months. Symptoms for 14 patients were from motor vehicle accident, of which 13 were in litigation. Patients attending physiotherapy over the course of treatment had better outcomes than those without physiotherapy. Women needed more injections (5.4) than men (3.2) p=0.0003. CONCLUSION: Intraarticular RIT improved pain and function in this case series. The procedure appears safe, more effective than periarticular RIT, and lasted as long, or longer, than those patients with previous radiofrequency neurotomy. Concurrent physiotherapy helped reduce post-procedure neck stiffness. Future trials should consider gender when deciding how many treatments to administer. Litigation was not a barrier to recovery.

PMID: 17387354 [PubMed - indexed for MEDLINE]

Discrimination of Brugada syndrome patients from individuals with the saddle-back type ST-segment elevation using a marker of the standard 12-lead electrocardiography.

Circ J. 2007 Apr;71(4):546-9

Authors: Nakazawa K, Sakurai T, Kishi R, Takagi A, Osada K, Ryu S, Fujita S, Matsuda H, Ishikawa Y, Miyake F

BACKGROUND: In the clinical situation, the saddle-back (S-B) type is more frequently detected than the coved type. In the present study, the discrimination of Brugada syndrome from the S-B type individuals using a marker of the standard 12-lead electrocardiography (ECG) was attempted. METHODS AND RESULTS: The study group consisted of 55 individuals with the S-B type in whom pilsicainide provocation test (PLC test) was carried out. The time from the onset of the QRS wave in lead V(2) (IV (2)) to the peak of the late R-like wave in the QRS wave (PV(2)), and the time from IV(2) to the offset of the QRS wave in lead V(5) (EV(5)) were measured. The coved type was induced by the PLC test in 29 cases (N-C group), but not in the remaining 26 cases (N-N group). The (IV(2) -PV(2)) - (IV(2) - EV(5)) value before the PLS test was greater in the N-C group than in the N-N group. The negative predictive value of ;(IV(2) - PV(2)) - (IV(2) - EV(5)) > or =0' was 76.4% for the prediction of a positive PLC test. CONCLUSIONS: A ;(IV(2) - PV(2)) - (IV(2) - EV(5)) > or =0' is a useful ECG marker for the discrimination of Brugada syndrome in the S-B type individuals.

PMID: 17384457 [PubMed - indexed for MEDLINE]

Bacillus cereus strain 10-L-2 produces two arylamine N-acetyltransferases that transform 4-phenylenediamine into 4-aminoacetanilide.

J Biosci Bioeng. 2007 Feb;103(2):147-54

Authors: Mulyono , Takenaka S, Sasano Y, Murakami S, Aoki K

A bacterium, strain 10-L-2, that was isolated from soil and identified as Bacillus cereus grew well on medium containing 4-phenylenediamine and Polypepton. Strain 10-L-2 converted a wide variety of anilines, including 4-phenylenediamine, to their corresponding acetanilides. Growing cells acetylated a single amino group of 4-phenylenediamine to form 4-aminoacetanilide with a 97% molar yield, as shown by mass spectrometry and HPLC. Cell extracts exhibited arylamine N-acetyltransferase (NAT) activity toward 4-phenylenediamine. Two NATs, namely, NAT-a and NAT-b, were separated by DE52 column chromatography and were further purified and characterized. The subunit molecular masses of NAT-a and NAT-b were 31.0 and 27.5 kDa, respectively, as determined by SDS-PAGE analysis. The two enzymes had similar pH- and thermo-stabilities and were similarly affected by pH, temperature, and several reagents. The enzymes showed peak activity toward 5-aminosalicylic acid of the substrates tested, but they differed in substrate specificity. Only NAT-a had activity toward sulfamethazine. Although other wild-type bacterial cultures also synthesize NAT, the ability of strain 10-L-2 to convert and detoxify 4-phenylenediamine is much higher. This report provides the first evidence of two NATs in a eubacterium.

PMID: 17368397 [PubMed - indexed for MEDLINE]

Safety and effectiveness of intravenous regional anesthesia (Bier block) for outpatient management of forearm trauma.

CJEM. 2006 Jul;8(4):247-50

Authors: Mohr B

OBJECTIVE: To assess the safety and effectiveness of intravenous regional anesthesia (Bier block) in the management of forearm injuries (i.e., forearm, wrist or hand) by primary care physicians at a diagnostic and treatment facility. METHODS: A retrospective review was conducted of all patients at a single centre who underwent a Bier block for forearm injuries between September 2000 and March 2005. RESULTS: 1816 Bier blocks were performed on 1804 patients (64% male) during the study period. Patient age ranged from 4-70 (mean 25) years. Wrist fractures requiring reduction were the most common diagnosis. Adverse events were recorded in 9 cases (0.50%, 95% confidence interval 0.23%-0.94%): 1 case of medication error (0.06%); 3 of improper cuff inflation (0.17%); and 5 of inadequate analgesia (0.28%). None of the adverse events resulted in failure to complete the procedure or in serious morbidity or mortality. CONCLUSION: Bier block anesthesia is a safe, effective and reliable technique in an outpatient primary care setting. This technique is a useful modality for physicians who manage acute upper-extremity injuries.

PMID: 17324303 [PubMed - indexed for MEDLINE]

Comparative study of the anesthetic efficacy of 4% articaine versus 2% lidocaine in inferior alveolar nerve block during surgical extraction of impacted lower third molars.

Med Oral Patol Oral Cir Bucal. 2007 Mar;12(2):E139-44

Authors: Sierra Rebolledo A, Delgado Molina E, Berini Ayt&#xED;s L, Gay Escoda C

BACKGROUND: A comparative study is made of the anesthetic efficacy of 4% articaine versus 2% lidocaine, both with epinephrine 1:100,000, in truncal block of the inferior alveolar nerve during the surgical extraction of impacted lower third molars. STUDY DESIGN: A randomized double-blind clinical trial was conducted of 30 patients programmed for the bilateral surgical extraction of symmetrical lower third molars in the context of the Master of Oral Surgery and Implantology (University of Barcelona, Barcelona, Spain). Following the obtainment of informed consent, two operators performed surgery on an extemporaneous basis, using as local anesthetic 4% articaine or 2% lidocaine with the same concentration of vasoconstrictor (epinephrine 1:100,000). The study variables for each anesthetic were: latency (time to action) and duration of anesthetic effect, the amount of anesthetic solution used, and the need of re-anesthetize the surgical zone. A visual analog scale was used to assess pain during surgery, and thus subjectively evaluate the anesthetic efficacy of the two solutions. RESULTS: Statistically significant differences (p = 0.003) were observed in the mean duration of anesthetic effect (220.86 min. for 4% articaine vs. 168.20 min. for 2% lidocaine). Latency, the amount of anesthetic solution and the need to re-anesthetize the surgical field showed clinical differences in favor of articaine, though statistical significance was not reached. The pain scores indicated similar anesthetic efficacy with both solutions. CONCLUSIONS: The results obtained suggest that 4% articaine offers better clinical performance than 2% lidocaine, particularly in terms of latency and duration of the anesthetic effect. However, no statistically significant differences in anesthetic efficacy were recorded between the two solutions.

PMID: 17322803 [PubMed - indexed for MEDLINE]

The contribution of refractoriness to arrhythmic substrate in hypokalemic Langendorff-perfused murine hearts.

Pflugers Arch. 2007 May;454(2):209-22

Authors: Sabir IN, Fraser JA, Killeen MJ, Grace AA, Huang CL

The clinical effects of hypokalemia including action potential prolongation and arrhythmogenicity suppressible by lidocaine were reproduced in hypokalemic (3.0 mM K(+)) Langendorff-perfused murine hearts before and after exposure to lidocaine (10 muM). Novel limiting criteria for local and transmural, epicardial, and endocardial re-excitation involving action potential duration (at 90% repolarization, APD(90)), ventricular effective refractory period (VERP), and transmural conduction time (Deltalatency), where appropriate, were applied to normokalemic (5.2 mM K(+)) and hypokalemic hearts. Hypokalemia increased epicardial APD(90) from 46.6 +/- 1.2 to 53.1 +/- 0.7 ms yet decreased epicardial VERP from 41 +/- 4 to 29 +/- 1 ms, left endocardial APD(90) unchanged (58.2 +/- 3.7 to 56.9 +/- 4.0 ms) yet decreased endocardial VERP from 48 +/- 4 to 29 +/- 2 ms, and left Deltalatency unchanged (1.6 +/- 1.4 to 1.1 +/- 1.1 ms; eight normokalemic and five hypokalemic hearts). These findings precisely matched computational predictions based on previous reports of altered ion channel gating and membrane hyperpolarization. Hypokalemia thus shifted all re-excitation criteria in the positive direction. In contrast, hypokalemia spared epicardial APD(90) (54.8 +/- 2.7 to 60.6 +/- 2.7 ms), epicardial VERP (84 +/- 5 to 81 +/- 7 ms), endocardial APD(90) (56.6 +/- 4.2 to 63.7 +/- 6.4 ms), endocardial VERP (80 +/- 2 to 84 +/- 4 ms), and Deltalatency (12.5 +/- 6.2 to 7.6 +/- 3.4 ms; five hearts in each case) in lidocaine-treated hearts. Exposure to lidocaine thus consistently shifted all re-excitation criteria in the negative direction, again precisely agreeing with the arrhythmogenic findings. In contrast, established analyses invoking transmural dispersion of repolarization failed to account for any of these findings. We thus establish novel, more general, criteria predictive of arrhythmogenicity that may be particularly useful where APD(90) might diverge sharply from VERP.

PMID: 17295037 [PubMed - indexed for MEDLINE]

Practice tips. Knee joint injections and aspirations: the triangle technique.

Can Fam Physician. 2006 Nov;52(11):1403-4

Authors: Lockman LE

PMID: 17279197 [PubMed - indexed for MEDLINE]

Antinociceptive effect of lidocaine in rats.

Pharmacol Rep. 2006 Nov-Dec;58(6):961-5

Authors: Rykaczewska-Czerwi&#x144;ska M

Lidocaine, a local anesthetic drug, exerts its effect by blocking sodium channels in peripheral sensory neurons. It is commonly used in clinical practice as a local anesthetic drug. This study was undertaken in order to determine the effect of lidocaine on sodium channels in neurons of the central nervous system and its modulatory effect on the pain perception in rats. Therefore, the effect of direct lidocaine administration icv on pain perception in rats exposed to noxious thermal stimuli was determined. A significant long-lasting antinociceptive effect of lidocaine injected at the doses ranging between 0.065-1.3 micromol (17.5-351 microg, respectively) was documented. It was concluded that intracerebral administration of sodium channel blockers might be a useful method in the study of pain perception in the brain.

PMID: 17220556 [PubMed - indexed for MEDLINE]

Evaluation of three topical anaesthetic agents against pain: a clinical study.

Indian J Dent Res. 2006 Oct-Dec;17(4):155-60

Authors: Nayak R, Sudha P

AIM: To compare pain responses of children during local anaesthetic infiltration at bilateral buccal sites prepared with topical application of EMLA 5% cream, benzocaine 18% gel or lignocaine 5% ointment and also to find out the rapidity of onset of action of these agents. METHODS: 60 healthy children aged 6 to 12 years old, received bilateral buccal infiltration following application of topical anaesthetic agents applied in a double blind design. Pain responses were compared based on subject self report using visual analogue scale (VAS) and operator assessment using Sound -Eye -Motor (SEM) scale. RESULTS: Benzocaine gel had the rapidest onset of action. EMLA 5% cream proved to be superior in pain reduction compared to benzocaine and lignocaine. Taste acceptance was better with benzocaine gel. Further studies are required for EMLA cream with an improved formulation more suitable for mucosal application before its routine use in dentistry.

PMID: 17217210 [PubMed - indexed for MEDLINE]

Gene expression profile in liver of differing ages of rats after single oral administration of acetaminophen.

J Toxicol Sci. 2006 Dec;31(5):491-507

Authors: Morishita K, Mizukawa Y, Kasahara T, Okuyama M, Takashima K, Toritsuka N, Miyagishima T, Nagao T, Urushidani T

In order to verify the influence of the rat age on hepatotoxicity, male Sprague-Dawley rats of 6 (young) and 12 (adult) weeks of age were orally administered acetaminophen (APAP), isoniazid (INH), or carbon tetrachloride (CCl4). Liver samples were obtained in a time-course manner, and changes in gene expression examined by an Affymetrix GeneChip. APAP caused more prominent hepatic injury with respect to pathology and blood biochemistry in adults than in young rats, whereas no obvious age-related differences were observed in INH- or CCl4-treated rats. Comparing gene expression in control rats, CYP3A13 was higher and GSTY2c was lower in adults, suggesting that production of the active metabolite of APAP is higher and its detoxification is lower in adults. The total amount of glutathione and total SH in rat liver was found to be higher in adult rats whereas the extent of its reduction by APAP was larger in adults. A detailed analysis of genes showing age-related differences revealed that some of them were different not in their extent but in their time course, i.e., the stress responses occurred earlier in the young than in the adult, resulting in a difference at 24 hr after dosing. These results suggest that the age-related difference in toxicity would be attributed to a higher expression of CYP3A13, producing the active metabolite of APAP as well as the lower expression of the detoxification enzyme, GSTY2c, in adult rats. Furthermore, these differences affect the time course of APAP toxicity. The present study clearly depicts the advantage of the multi-time, multi-dose protocol employed in our project for analyzing the mechanism of toxicity by gene expression profiling.

PMID: 17202762 [PubMed - indexed for MEDLINE]

Genomic cluster and network analysis for predictive screening for hepatotoxicity.

J Toxicol Sci. 2006 Dec;31(5):419-32

Authors: Fukushima T, Kikkawa R, Hamada Y, Horii I

The present study was undertaken to estimate the usefulness of genomic approaches to predict hepatotoxicity. Male rats were treated with acetaminophen (APAP), carbon tetrachloride (CCL), amiodarone (AD) or tetracycline (TC) at toxic doses. Their livers were extracted 6 or 24 hr after the dosings and were used for subsequent examinations. At 6 hr there were no histological changes noted in any of the groups except for the CCL group, but at 24 hr, such changes were noted in all but the AD group. Regarding genomic analysis, we performed hierarchical cluster analysis using S-plus software. The individual microarray data were clearly classified into 5 treatment-related clusters at 24 hr as well as at 6 hr, even though no morphological changes were noted at 6 hr. In the gene expression analysis using GeneSpring, transcription factor and oxidative stress- and lipid metabolism-related genes were markedly affected in all treatment groups at both time points when compared with the corresponding control values. Finally, we investigated gene networks in the above-affected genes by using Ingenuity Pathway Analysis software. Down-regulation of lipid metabolism-related genes regulated by SREBP1 was observed in all treatment groups at both time points, and up-regulation of oxidative stress-related genes regulated by Nrf2 was observed in the APAP and CCL treatment groups. From the above findings, for the application of genomic approaches to predict hepatotoxicity, we considered that cluster analysis for classification and early prediction of hepatotoxicity and network analysis for investigation of toxicological biomarkers would be useful.

PMID: 17202758 [PubMed - indexed for MEDLINE]