The combination of oral lysine-acetylsalicylate and metoclopramide compared with oral sumatriptan in the treatment of migraine attacks. A randomized, double-blind, placebo-controlled clinical trial

A combination of lysine acetylsalicylate (equivalent to 900 mg aspirin) and 10 mg metoclopramide (LAS + MTC) was compared with oral sumatriptan (100 mg) and placebo in 421 patients with migraine in a randomized, double-blind, clinical trial. LAS + MTC was as effective as sumatriptan with a decrease in headache from severe or moderate to mild or none in 57% and 53%, respectively, for the first migraine attack treated, the primary efficacy parameter. Both treatments were better than placebo (success rate 24%, p < 0.001). LAS + MTC was better tolerated than sumatriptan (adverse events in 18% and 28%, respectively, p < 0.05).     

Postoperative analgesia in herniated disk surgery. Comparative study of diclofenac , lysine acetylsalicylate, and ketorolac

INTRODUCTION: Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective in treating musculoskeletal pain and are theoretically ideal for treating postoperative pain of the lumbar column. OBJECTIVES: To compare the analgesic efficacy and side effects of treatment with 3 NSAIDs (lysine acetylsalicylate, ketorolac and diclofenac) in the treatment of pain after surgery for lumbar disc hernia. PATIENTS AND METHODS: We enrolled 75 ASA I-II patients undergoing discectomy because of lumbar disc hernia; balanced general anesthesia was used in all cases. The patients were randomly distributed in 3 groups based on type of analgesia given in the immediate postoperative period. Group A received lysine acetylsalicylate (1800 mg), group B received ketorolac (30 mg) and group C received diclofenac (75 mg). The analgesics were diluted in 100 mg of saline solution and administered through a peripheral vein over 10 min. We evaluated the analgesia attained on a visual analog scale (VAS) and the physiological response to pain was assessed by monitoring changes in arterial pressure, heart rate and breathing frequency. If analgesia was insufficient 30 min after administration of the drug, 200 mg of lysine cloximate was given as a top-up. The side effects of each drug were also recorded. RESULTS: VAS evaluation showed significant reductions in pain 60 min after administration in groups A and B and after 120 min in group C. Nine patients in each group required lysine cloximate. There were no significant differences in physiological response among the 3 groups. No patient suffered major side effects. Mild side effects were reported most often in group B. CONCLUSIONS: The NSAIDs studied were inadequately for treating pain after surgery for lumbar disc hernia. Ketorolac was no better than the other analgesics studied but was associated with a higher number of mild side effects.     

Serotonin receptors and the acute attack of migraine

The concept of nursing expertise has been the focus of considerable debate since the early 1980s, yet an agreed definition of the concept and the precise criteria by which it can be evaluated remains elusive. This paper will describe an exploratory study into A & E nurses' constructs of the nature of nursing expertise. Seven first level Accident and Emergency (A & E) nurses were interviewed using Kelly's Repertory Grid Technique. Each was asked to provide examples of nurses with whom they are working or have worked, to match eight given examples designed to represent varying levels of clinical expertise. The informants were asked to consider in what way two of their chosen examples were alike and differed from a third in their clinical practice. A total of 55 bi-polar constructs emerged which were clustered under four main headings. These suggested that A & E nurses perceived expert practice to be characterized by a high level of empirical knowledge, supportive team building, assertive clinical leadership and patient-focused involvement.     

Sumatriptan in the acute treatment of migraine without aura: efficacy of 50-mg dose

We conducted an open study on the efficacy of 50 mg of sumatriptan as an acute treatment for migraine without aura. We recruited 200 consecutive patients, with an established history of migraine without aura, presenting at a headache center. The patients were instructed to take half a 100-mg sumatriptan tablet for their next migraine attack, and to record details of their headache in a diary. The primary outcome of the study was headache relief from one migraine attack. Attacks were moderately intense (46%), moderate to severe (7%), or severe (47%). Total or partial benefit at 2 hours from the 50-mg dose was reported by 140 of 200 patients (70%). Thirty-six patients received no benefit from half a tablet, and 24 did not take sumatriptan, preferring their habitual medication. Side effects were few, mild, and short lasting. We conclude that the 50-mg oral dose is generally effective for migraine without aura attacks of both moderate and severe intensity and recommend this dose for all such patients. If, however, sumatriptan is ineffective at that dose it can be increased to a maximum of 100 mg.     

Sulpiride in the prophylactic treatment of migraine

The aim of the work was investigation of both efficacy of sulpiride, atypical neuroleptic drug with pronounced antidepressive activity, and its influence on central nervous system. The study was performed in the course of prophylactic treatment of migraine using contingent negative variation (CNV) index. It is demonstrated that sulpiride is effective in prophylactic treatment of migraine complicated with psychologic disorders and autonomic dysfunctions. Such effect may be caused by the drug's influence on depression, anxiety, autonomic symptoms, tension-type headaches. This conclusion was confirmed by CNV data, change of which after sulpiride administration have indicated normalization of mental performance and increase of active adaptive abilities.     

A multicenter, investigator-blinded, randomized comparison of oral levofloxacin and oral clarithromycin in the treatment of acute bacterial sinusitis

The effects of Vitamin E administration on antioxidant enzyme activities and nitrite-nitrate levels of the reperfused rat kidney tissues were investigated by performing a 60 min ischemia followed by 24 and 72 hours of reperfusion. Vitamin E administration or the placebo (SF) was applied as 100 mg/kg BW. As expected, catalase (CAT) (p<0.05) and superoxide dismutase (SOD) (p<0.05) activities of ischemia/reperfused (I/R) kidney tissue were lower and malondialdehyde (MDA) levels were higher than control kidneys in both SF and vitamin E treated groups following 24 h reperfusion. During reperfusion of long term (72 h), vitamin E triggered a decrease in the MDA levels in the ischemic tissue, while it did not provoke a significant effect on SOD and catalase activities. Total nitrite levels of ischemic tissues in both of the groups were higher than matched control kidneys and this elevation was more clear in the vitamin E treated group. Our results showed that vitamin E has a protective effect on I/R injury, by a direct chain breaking effect on lipid peroxidation (LPO) and hence preventing the nitric oxide (NO) reservoir of ischemic tissue. Alfa-tocopherol may be a promising agent for the prevention of tissue injury caused by free oxygen radicals.     

Repeated treatment with high doses of morphine produces comparable tolerance to low- and high-dose discriminative stimulus effects of morphine.

Morphine tolerance was studied in 9 pigeons (Columba livia, N?=?9) trained to discriminate among a low dose of morphine (1.8 mg/kg), a high dose of morphine (10 mg/kg), and saline. Doses of morphine required for low-dose or high-dose stimulus effects were determined before, during, and after a 4-week treatment period, during which training was suspended. Treatment with 56 mg/kg, but not 10 mg/kg, morphine, b.i.d., increased the doses required for either low-dose or high-dose stimulus effects by approximately 10-fold. Both treatments increased doses required for rate suppression. Sensitivity recovered after a week of saline treatment. Acute treatment with 56 mg/kg morphine did not change sensitivity. These results suggest that chronic morphine treatment can produce surmountable, reversible tolerance to morphine acting as a discriminative stimulus, without disrupting a discrimination between low-dose and high-dose stimulus effects. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Subcutaneous sumatriptan in the acute treatment of migraine in patients using dihydroergotamine as prophylaxis. French Migraine Network Bordeaux-Lyon-Grenoble

The efficacy of sumatriptan, a 5-HT1 receptor agonist, in patients with migraine attacks occurring despite prophylactic treatment with oral dihydroergotamine, was assessed in a double-blind placebo-controlled study involving 76 patients. Thirty-seven patients were treated with a subcutaneous injection of 6 mg sumatriptan self-administered with an auto-injector and 39 with placebo given by the same route. Patients having inadequate relief were allowed to use a second injection of test medication 1 hour later and rescue treatment between 2 hours and 24 hours after the first dose. Headache relief was achieved within 2 hours after sumatriptan in 26 patients (70%) compared to 8 patients (21%) in the placebo group (P < 0.0001). Of these patients, 19 (51%) and 3 (8%) were, respectively, pain free at this time. A second injection of sumatriptan was used by 8 (22%) patients compared to 30 (77%) patients in the placebo group (P < 0.0001), whereas rescue medication was used respectively by 13 (35%) and 22 (58%) patients (P < 0.024). The adverse event profile of sumatriptan was not affected by the concomitant use of dihydroergotamine and side-effects were all minor and transient. Patient satisfaction was significantly higher in the sumatriptan group (75%) compared to patient satisfaction with placebo (16%). These results show that the high efficacy rate of subcutaneous sumatriptan and its safety profile remain unchanged in migraine patients receiving oral dihydroergotamine as prophylaxis.     

Effects of combined treatment with glycopyrrolate and albuterol in acute exacerbation of asthma

STUDY OBJECTIVE: Recent reports suggest that glycopyrrolate is as effective as metaproterenol in the treatment of acute bronchospasm. The purpose of this study was to investigate whether the addition of a single aerosolized dose of glycopyrrolate to an albuterol regimen results in a greater improvement in pulmonary function than treatment with an albuterol regimen alone in patients with acute asthma. DESIGN: Prospective, randomized, double-blinded, controlled study. All patients received a total of three aerosol treatments and 60 mg solumedrol IV push. Patients were randomized to receive 2 mg aerosolized glycopyrrolate (combination therapy) or aerosolized placebo (control) in addition to their first 2.5 mg albuterol aerosol treatment. Both groups received 2.5 mg aerosolized albuterol alone for the next two treatments. SETTING: An urban teaching hospital emergency department. PARTICIPANTS: One hundred twenty-five patients with acute exacerbation of asthma were entered into the study. MAIN RESULTS: There was no difference in pretreatment forced expiratory volume (one second) (FEV1) between the control group and the glycopyrrolate group. Asthmatic patients receiving combination therapy had less of a change in FEV1 (52%) than did control patients (82%, P < .05). CONCLUSION: The combination of glycopyrrolate and albuterol does not appear to be beneficial over albuterol alone in treating patients with acute exacerbation of asthma.     

Valproic acid in prophylactic treatment of migraine

AIM: To determine whether an oral tetravalent rotavirus vaccine (RV-TV) can be safely coadministered with a combined diphtheria-tetanus-pertussis-Haemophilus influenzae type b vaccine (DTP/Hib) and oral poliovirus vaccine (OPV) to healthy infants without interfering with the immune responses to any of the component antigens. METHODS: Two hundred sixty-seven infants ages 2 to 3 months were randomly assigned in a double blind fashion to receive three doses of either placebo or RV-TV, each containing 4 x 10(5) plaque-forming units, concurrently with DTP/ Hib (Tetramune) and OPV at approximately 2, 4 and 6 months of age. Infants were followed for 5 days after each dose for the occurrence of adverse events and subsequently until 3 to 6 weeks after the third dose of RV-TV or placebo. Immune responses were assessed by measuring the postvaccination serum antibody titers to each component of DTP/ Hib and OPV at 3 to 6 weeks after the third dose. RESULTS: The percentage of infants who attained protective antibody titers and the distribution of antibody titers against diphtheria toxoid, tetanus toxoid and H. influenzae type b were not statistically different between RV-TV and placebo recipients. The distribution of antibody titers against different antigens of Bordetella pertussis (agglutinins, pertussis toxoid, filamentous hemagglutinin, fimbriae antigens and the 69-kDa outer membrane protein) was compared and no significant differences were found. The percentage of infants with detectable neutralizing antibodies against the three serotypes of poliovirus and the distribution of antibody titers was not statistically different between RV-TV and placebo recipients. There were no clinically meaningful differences in postvaccination reactions between RV-TV and placebo recipients. CONCLUSIONS: Three doses of RV-TV can be safely coadministered with three doses of DTP/ Hib and OPV without diminishing an infant's serum antibody responses to each component of these vaccines. Therefore RV-TV can be given at the standard childhood visits at 2, 4 and 6 months of age.     

Repeated sessions of sleep deprivation in the treatment of depression

30 depressed patients were submitted to repeated sessions of sleep deprivation. The results obtained in a previous study were confirmed: after 36 hours of wakefulness there is an important overall improvement, albeit followed by a partial or total relapse the second day after. There are no counter-indications, even for elderly subjects with psycho-organic symptoms.     

The pharmacokinetics of ephedrine after oral dosage in asthmatics receiving acute and chronic treatment

1 Ephedrine plasma levels have been measured in ten asthmatic patients given a singel dose of ephedrine hydrochloride (22 mg) along and in combination with theophylline and a barbiturate. 2 Pharmacokinetic assessment of the data indicated no significant intra-subject changes in kinetic parameters before or after chronic treatment with ephedrine HCl (11 mg three times a day) alone or in combination. 3 Tolerance to these therapeutic doses, if it occurs, is therefore not disposition-related but rather to pharmacodynamic changes.     

Efficacy of oral pyronaridine for the treatment of acute uncomplicated falciparum malaria in African children

Pyronaridine is a new antimalarial agent developed in China. In this randomized, unblinded study, the safety, tolerance, and clinical efficacy of pyronaridine (n = 44) were evaluated and compared with those of chloroquine (n = 44), the standard first-line antimalarial drug in most of Africa, in 88 Cameroonian children with acute uncomplicated falciparum malaria. The target sample size was determined to detect a 35% difference in in vivo resistance between the two treatment groups, with 95% power. Clinical and parasitological responses were monitored for 14 days on an outpatient basis. Seven children (3 treated with pyronaridine and 4 treated with chloroquine) were lost to follow-up and were excluded from the analysis. All 41 patients treated with pyronaridine were cured. Treatment failure was observed in 16 (40%) of the 40 children treated with chloroquine. In vitro assays indicated that 23 of 40 clinical isolates obtained from patients treated with pyronaridine were resistant in vitro to chloroquine. Side effects associated with pyronaridine intake were minor and transient. Pyronaridine is safe and well tolerated by symptomatic Cameroonian children, and it is highly efficacious in Africa, where chloroquine resistance is well established.     

Mucosa-adhesive water-soluble polymer film for treatment of acute radiation-induced oral mucositis

The betagamma subunits of G proteins were coimmunoprecipitated with antibodies against various alpha subunits, and analyzed by silver stain and immunoblotting with conventional transfer procedure and membrane-blocking buffer containing 2% BSA. Multiple isoforms of gamma were coimmunoprecipitated with no significant difference in form or ratio among the antibodies against alpha subunits used, suggesting antibodies against any alpha subunit could coimmunoprecipitate all forms of gamma. Therefore, this method was applicable to analyze gamma subunits in various cells, especially to clarify what forms of gamma subunits are major components. The major isoforms were: gamma5 in C6, NG108-15, HeLa, HEK293, and F9 cells; gamma12 in Swiss 3T3 and BRL-3A cells; and gamma3 in PC12 cells. In addition to most gamma subunits identified, unidentified gamma subunits were present in PC12, NG108-15, and BRL-3A cells. Furthermore, the method was applied to examine changes of isoforms of gamma during differentiation of HL-60 cells. Undifferentiated cells mainly contained gamma5, but retinoic acid treatment of cells replaced most gamma5 with gamma2. Thus, this method is useful to determine the major isoforms which seem to be the more important in cells.     

The treatment of pain trigger areas in migraine

In many patients with migraine, several localised areas usually on the scalp or neck can be identified. The local injection of lignocaine one per cent and adrenaline 1/200,000 often leads to considerable relief of the symptoms of migraine including visual phenomena. The common sites of the trigger areas are shown and several uncontrolled case reports of the effect of the treatment are described.     

Bioavailability and pharmacokinetics of beta-methyldigoxin after multiple oral and intravenous doses

To obtain true half lives, glycoside elimination from six healthy subjects was studied for 14 days after multiple intravenous doses or oral administration of a daily maintenance dose of beta-methyldigoxin 0.3 mg. After oral or intravenous administration of beta-methyldigoxin ceased, the plasma concentrations declined from the 14th to the 16th days with a half life of 1.7 days. From the 16th to the 20th day a change from a shorter to a longer half life of 2.8 and 2.9 days was observed. Similar half lives were found in urine: after the last dose the initial slope from the 14th to the 16th day had a half life of 1.8 days, and the terminal slope had one of 3.2 days. The results indicate release of the glycoside from slowly equilibrating tissues.     

Intramuscular ceftriaxone compared with oral amoxicillin-clavulanate for treatment of acute otitis media in children

Two hundred and fifteen children aged 4 months 6 years with acute otitis media (AOM) were randomized to be treated either by a single i.m. injection of ceftriaxone, 50 mg/kg, with a second dose in the event of unsatisfactory response after 48 h or a history of recurrent AOM (109 patients) or amoxicillin clavulanate 12.5 mg tid (106 patients). The failure rate was similar in children treated by ceftriaxone and amoxicillin clavulanate, 4.6% and 4.7%, respectively (standard error for intergroup difference -2.87%, 95% confidence interval -5.62% to 5.87%). No significant differences between the groups were found in the dynamics of the resolution of the acute symptomatology, otoscopy findings, relapse rate at 30 days or tympanographic evidence of middle ear effusion at the scheduled visits on days 30, 60 and 90. Recurrence of AOM between days 31 and 90 was observed significantly in more children treated with amoxicillin clavulanate than with ceftriaxone--25 out of 84 (29.4%) versus 11 out of 81 (13.6%) (P = 0.012). Conclusion: Ceftriaxone injection(s) is as efficient at least as 10-day oral amoxicillin clavulanate for treatment of acute otitis media in children. Although not recommended as routine, ceftriaxone can be considered in the management of acute otitis media under special circumstances, particularly in cases when the ability to tolerate or absorb oral drugs is compromised, in children refusing or unable to take oral therapy or when the compliance is questionable.