Multiple drug-delivery strategies to enhance the pharmacological and toxicological properties of Mefenamic acid.

OBJECTIVE: To improve the biological and toxicological properties of Mefenamic acid (MA), the galactosylated prodrug of MA named MefeGAL was included in polymeric solid dispersions (PSs) composed of poly(glycerol adipate) (PGA) and Pluronic® F68 (MefeGAL-PS). MefeGAL-PS was compared with polymeric solid formulations of MA (MA-PS) or a mixture of equal ratio of MefeGAL/MA (Mix-PS). METHODS: The in vitro and in vivo pharmacological and toxicological profiles of PSs have been investigated. In detail, we evaluated the anti-inflammatory (carrageenan-induced paw edema test), analgesic (acetic acid-induced writhing test) and ulcerogenic activity in mice after oral treatment. Additionally, the antiproliferative activity of PSs was assessed on in vitro models of colorectal and non-small cell lung cancer. RESULTS: When the PSs were resuspended in water, MefeGAL's, MA's and their mixture's apparent solubilities improved due to the interaction with the polymeric formulation. By comparing the in-vivo biological performance of MefeGAL-PS with that of MA, MefeGAL and MA-PS, it was seen that MefeGAL-PS exhibited the same sustained and delayed analgesic and anti-inflammatory profile as MefeGAL but did not cause gastrointestinal irritation. The pharmacological effect of Mix-PS was present from the first hours after administration, lasting about 44 hours with only slight gastric mucosa irritation. In-vitro evaluation indicated that Mix-PS had statistically significant higher cytotoxicity than MA-PS and MefeGAL-PS. CONCLUSIONS: These preliminary data are promising evidence that the galactosylated prodrug approach in tandem with a polymer-drug solid dispersion formulation strategy could represent a new drug delivery route to improve the solubility and biological activity of NSAIDs.

Progestogen-releasing intrauterine systems for heavy menstrual bleeding.

BACKGROUND: Heavy menstrual bleeding (HMB) impacts the quality of life of otherwise healthy women. The perception of HMB is subjective and management depends upon, among other factors, the severity of the symptoms, a woman's age, her wish to get pregnant, and the presence of other pathologies. Heavy menstrual bleeding was classically defined as greater than or equal to 80 mL of blood loss per menstrual cycle. Currently the definition is based on the woman's perception of excessive bleeding which is affecting her quality of life. The intrauterine device was originally developed as a contraceptive but the addition of progestogens to these devices resulted in a large reduction in menstrual blood loss: users of the levonorgestrel-releasing intrauterine system (LNG-IUS) reported reductions of up to 90%. Insertion may, however, be regarded as invasive by some women, which affects its acceptability. OBJECTIVES: To determine the effectiveness, acceptability and safety of progestogen-releasing intrauterine devices in reducing heavy menstrual bleeding. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL (from inception to June 2019); and we searched grey literature and for unpublished trials in trial registers. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in women of reproductive age treated with LNG-IUS devices versus no treatment, placebo, or other medical or surgical therapy for heavy menstrual bleeding. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data, assessed risk of bias and conducted GRADE assessments of the certainty of evidence. MAIN RESULTS: We included 25 RCTs (2511 women). Limitations in the evidence included risk of attrition bias and low numbers of participants. The studies compared the following interventions. LNG-IUS versus other medical therapy The other medical therapies were norethisterone acetate, medroxyprogesterone acetate, oral contraceptive pill, mefenamic acid, tranexamic acid or usual medical treatment (where participants could choose the oral treatment that was most suitable). The LNG-IUS may improve HMB, lowering menstrual blood loss according to the alkaline haematin method (mean difference (MD) 66.91 mL, 95% confidence interval (CI) 42.61 to 91.20; 2 studies, 170 women; low-certainty evidence); and the Pictorial Bleeding Assessment Chart (MD 55.05, 95% CI 27.83 to 82.28; 3 studies, 335 women; low-certainty evidence). We are uncertain whether the LNG-IUS may have any effect on women's satisfaction up to one year (RR 1.28, 95% CI 1.01 to 1.63; 3 studies, 141 women; I² = 0%, very low-certainty evidence). The LNG-IUS probably leads to slightly higher quality of life measured with the SF-36 compared with other medical therapy if (MD 2.90, 95% CI 0.06 to 5.74; 1 study: 571 women; moderate-certainty evidence) or with the Menorrhagia Multi-Attribute Scale (MD 13.40, 95% CI 9.89 to 16.91; 1 trial, 571 women; moderate-certainty evidence). The LNG-IUS and other medical therapies probably give rise to similar numbers of women with serious adverse events (RR 0.91, 95% CI 0.63 to 1.30; 1 study, 571 women; moderate-certainty evidence). Women using other medical therapy are probably more likely to withdraw from treatment for any reason (RR 0.49, 95% CI 0.39 to 0.60; 1 study, 571 women, moderate-certainty evidence) and to experience treatment failure than women with LNG-IUS (RR 0.34, 95% CI 0.26 to 0.44; 6 studies, 535 women; moderate-certainty evidence). LNG-IUS versus endometrial resection or ablation (EA) Bleeding outcome results are inconsistent. We are uncertain of the effect of the LNG-IUS compared to EA on rates of amenorrhoea (RR 1.21, 95% CI 0.85 to 1.72; 8 studies, 431 women; I² = 21%; low-certainty evidence) and hypomenorrhoea (RR 0.98, 95% CI 0.73 to 1.33; 4 studies, 200 women; low-certainty evidence) and eumenorrhoea (RR 0.55, 95% CI 0.30 to 1.00; 3 studies, 160 women; very low-certainty evidence). We are uncertain whether both treatments may have similar rates of satisfaction with treatment at 12 months (RR 0.95, 95% CI 0.85 to 1.07; 5 studies, 317 women; low-certainty evidence). We are uncertain if the LNG-IUS compared to EA has any effect on quality of life, measured with SF-36 (MD -14.40, 95% CI -22.63 to -6.17; 1 study, 33 women; very low-certainty evidence). Women with the LNG-IUS compared with EA are probably more likely to have any adverse event (RR 2.06, 95% CI 1.44 to 2.94; 3 studies, 201 women; moderate-certainty evidence). Women with the LNG-IUS may experience more treatment failure compared to EA at one year follow up (persistent HMB or requirement of additional treatment) (RR 1.78, 95% CI 1.09 to 2.90; 5 studies, 320 women; low-certainty evidence); or requirement of hysterectomy may be higher at one year follow up (RR 2.56, 95% CI 1.48 to 4.42; 3 studies, 400 women; low-certainty evidence). LNG-IUS versus hysterectomy We are uncertain whether the LNG-IUS has any effect on HMB compared with hysterectomy (RR for amenorrhoea 0.52, 95% CI 0.39 to 0.70; 1 study, 75 women; very low-certainty evidence). We are uncertain whether there is difference between LNG-IUS and hysterectomy in satisfaction at five years (RR 1.01, 95% CI 0.94 to 1.08; 1 study, 232 women; low-certainty evidence) and quality of life (SF-36 MD 2.20, 95% CI -2.93 to 7.33; 1 study, 221 women; low-certainty evidence). Women in the LNG-IUS group may be more likely to have treatment failure requiring hysterectomy for HMB at 1-year follow-up compared to the hysterectomy group (RR 48.18, 95% CI 2.96 to 783.22; 1 study, 236 women; low-certainty evidence). None of the studies reported cost data suitable for meta-analysis. AUTHORS' CONCLUSIONS: The LNG-IUS may improve HMB and quality of life compared to other medical therapy; the LNG-IUS is probably similar for HMB compared to endometrial destruction techniques; and we are uncertain if it is better or worse than hysterectomy. The LNG-IUS probably has similar serious adverse events to other medical therapy and it is more likely to have any adverse events than EA.

Comparison of Intra-Socket Bupivacaine Administration Versus Oral Mefenamic Acid Capsule for Postoperative Pain Management Following Removal of Impacted Mandibular Third Molars.

PURPOSE: Surgical removal of impacted third molar teeth is one of the most common surgical procedures performed in oral and maxillofacial surgery. Postoperative pain is a common and predictable occurrence after maxillofacial surgery. MATERIALS AND METHODS: This randomized double-blind clinical trial was conducted with a crossover design in which each patient served as his or her own control. Forty-six patients with similar bilateral impacted lower third molars were selected. In each patient, the intervention and control sides of the mandible were randomly determined at the end of surgery. If the removed tooth was in the intervention side, then the patient would receive bupivacaine and a placebo of mefenamic acid. If the impacted tooth was in the control side, then the patient would receive a mefenamic acid capsule and a placebo of bupivacaine. Pain severity was assessed using a visual analog scale. Data were analyzed using paired-sample t test and a P value less than .05 was considered statistically significant. RESULTS: Of 46 participants originally recruited, 43 were included in the present study. The mean postoperative pain score in patients who received bupivacaine was increased to a maximum 4 hours, with marked improvements after this time. The mean intensity of pain after administration of bupivacaine was lower than that of mefenamic acid capsules at different time points. Statistical analysis showed a relevant difference in pain intensity between the 2 study groups. CONCLUSION: The results of the present study showed that local administration of bupivacaine relieves postoperative pain after surgical removal of impacted third molar teeth.

Mefenamic acid enhances anticancer drug sensitivity via inhibition of aldo-keto reductase 1C enzyme activity.

Resistance to anticancer medications often leads to poor outcomes. The present study explored an effective approach for enhancing chemotherapy targeted against human cancer cells. Real-time quantitative real-time polymerase chain reaction (qRT-PCR) analysis revealed overexpression of members of aldo-keto reductase (AKR) 1C family, AKR1C1, AKR1C2, AKR1C3, and AKR1C4, in cisplatin, cis-diamminedichloroplatinum (II) (CDDP)-resistant human cancer cell lines, HeLa (cervical cancer cells) and Sa3 (oral squamous cell carcinoma cells). The genes were downregulated using small-interfering RNA (siRNA) transfection, and the sensitivity to CDDP or 5-fluorouracil (5-FU) was investigated. When the genes were knocked down, sensitivity to CDDP and 5-FU was restored. Furthermore, we found that administration of mefenamic acid, a widely used non-steroidal anti-inflammatory drug (NSAID) and a known inhibitor of AKR1Cs, enhanced sensitivity to CDDP and 5-FU. The present study suggests that AKR1C family is closely associated with drug resistance to CDDP and 5-FU, and mefenamic acid enhances their sensitivity through its inhibitory activity in drug-resistant human cancer cells. Thus, the use of mefenamic acid to control biological function of AKR1C may lead to effective clinical outcomes by overcoming anticancer drug resistance.

Cryomilling-induced solid dispersion of poor glass forming/poorly water-soluble mefenamic acid with polyvinylpyrrolidone K12.

The effect of mechanical impact on the polymorphic transformation of mefenamic acid (MFA) and the formation of a solid dispersion of mefenamic acid, a poor glass forming/poorly-water soluble compound, with polyvinylpyrrolidone (PVP) K12 was investigated. The implication of solid dispersion formation on solubility enhancement of MFA, prepared by cryomilling, was investigated. Solid state characterization was conducted using powder X-ray diffraction (PXRD) and Fourier-transform infrared (FTIR) spectroscopy combined with crystal structure analysis. Apparent solubility of the mixtures in pH 7.4 buffer was measured. A calculation to compare the powder patterns and FTIR spectra of solid dispersions with the corresponding physical mixtures was conducted. Solid state characterization showed that (1) MFA I transformed to MFA II when pure MFA I was cryogenically milled (CM); and (2) MFA forms a solid dispersion when MFA was cryogenically milled with PVP K12. FTIR spectral analysis showed that hydrogen bonding facilitated by mechanical impact played a major role in forming solid dispersions. The apparent solubility of MFA was significantly improved by making a solid dispersion with PVP K12 via cryomilling. This study highlights the importance of cryomilling with a good hydrogen bond forming excipient as a technique to prepare solid dispersion, especially when a compound shows a poor glass forming ability and therefore, is not easy to form amorphous forms by conventional method.

Formulation and evaluation of mefenamic acid sustained release matrix pellets.

The objective of the study was to prepare mefenamic acid (MA) sustained release matrix pellets and investigate the formulation parameters affecting pellet attributes and drug release in vitro. Amixer torque rheometer (MTR) was used to characterize the rheological properties of wet mass used in pellet formulation. Mefenamic acid pellets were prepared by extrusion/spheronization techniques using microcrystalline cellulose (MCC) in combination with lactose as pellet forming agents and water as the binding liquid. Also, the prepared pellets were characterized for their particle size and in vitro drug dissolution. The results revealed that the increase in lactose weight ratio to MCC resulted in a significant reduction of both maximum torque and binder ratios, while the addition of 2 % (m/m) polyvinyl pyrolidone (PVP) to MCC-lactose influenced only the mean torque rather than the wetting liquid (water). Particle size ranged from 945 to 1089 mm and had small span values (0.56-0.67). Furthermore, an inverse relation was observed between the rheological character of pellet wet masses (expressed by peak torque) and in vitro release rate. Increasing MAloading from 2.5 to 5 and 10 % was accompanied by a decrease in dissolution rates. In conclusion, properties of MA matrix pellets could be successfully monitored by controlling the wet mass characteristics by measuring torque.

Effects of rifampin and mefenamic acid on the pharmacokinetics and pharmacodynamics of dapagliflozin.

AIMS: Dapagliflozin is a selective sodium glucose cotransporter 2 (SGLT2) inhibitor that decreases serum glucose by reducing renal glucose reabsorption, thereby promoting urinary glucose excretion. Dapagliflozin is primarily metabolized via the uridine diphosphate-glucuronosyltransferase (UGT)1A9 pathway to its major inactive metabolite, dapagliflozin 3-O-glucuronide. The aim of this study was to evaluate the potential for drug-drug interaction between dapagliflozin and two potential UGT1A9 modulators. METHODS: The results of two open-label, non-randomized, single-sequence studies are reported in which the effects of rifampin (a pleiotropic drug-metabolizing enzyme inducer; study 1) and mefenamic acid (a strong UGT1A9 inhibitor; study 2) were evaluated on the pharmacokinetics and pharmacodynamics (assessed by urinary glucose excretion [UGE]) of dapagliflozin in healthy subjects. In study 1, 14 subjects received single doses of dapagliflozin 10 mg alone and in the presence of rifampin 600 mg QD (6 days). In study 2, 16 subjects received single doses of dapagliflozin 10 mg alone and in the presence of mefenamic acid 250 mg q6h (5 days). RESULTS: Rifampin reduced total exposure (area under the concentration-time curve from time 0 to infinity [AUC0-inf]) to dapagliflozin by 22% and mefenamic acid increased dapagliflozin AUC0-inf by 51%. No clinically meaningful effect of rifampin or mefenamic acid on the pharmacokinetics of dapagliflozin or on dapagliflozin-mediated urinary glucose excretion was observed. CONCLUSION: Modest changes in dapagliflozin exposure were seen with rifampin and mefenamic acid with minor changes in UGE, none of which were considered clinically meaningful.

Single dose oral mefenamic acid for acute postoperative pain in adults.

BACKGROUND: Mefenamic acid is a non-steroidal anti-inflammatory drug (NSAID). It is most often used for treating pain of dysmenorrhoea in the short term (seven days or less), as well as mild to moderate pain including headache, dental pain, postoperative and postpartum pain. It is widely available in many countries worldwide. OBJECTIVES: To assess the efficacy of single dose oral mefenamic acid in acute postoperative pain, and any associated adverse events. SEARCH STRATEGY: We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to December 2010. SELECTION CRITERIA: Single oral dose, randomised, double-blind, placebo-controlled trials of mefenamic acid for relief of established moderate to severe postoperative pain in adults. DATA COLLECTION AND ANALYSIS: Studies were assessed for methodological quality and the data extracted by two review authors independently. Summed total pain relief (TOTPAR) or pain intensity difference (SPID) over 4 to 6 hours was used to calculate the number of participants achieving at least 50% pain relief. These derived results were used to calculate, with 95% confidence intervals, the relative benefit compared to placebo, and the number needed to treat (NNT) for one participant to experience at least 50% pain relief over 4 to 6 hours. Numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals was collected. MAIN RESULTS: Four studies with 842 participants met the inclusion criteria; 126 participants were treated with mefenamic acid 500 mg, 67 with mefenamic acid 250 mg, 197 with placebo, and 452 with lignocaine, aspirin, zomepirac or nimesulide. Participants had pain following third molar extraction, episiotomy and orthopaedic surgery. The NNT for at least 50% pain relief over 6 hours with a single dose of mefenamic acid 500 mg compared to placebo was 4.0 (2.7 to 7.1), and the NNT to prevent use of rescue medication over 6 hours was 6.5 (3.6 to 29). There were insufficient data to analyse other doses or active comparators, or numbers of participants experiencing any adverse events. No serious adverse events or adverse event withdrawals were reported in these studies. AUTHORS' CONCLUSIONS: Oral mefenamic acid 500 mg was effective at treating moderate to severe acute postoperative pain, based on limited data. Efficacy of other doses, and safety and tolerability could not be assessed.

Transnasal butorphanol for pain relief after uvulopalatopharyngoplasty - a hospital-based,randomized study.

BACKGROUND: Nasal spray of analgesic is a novel administration for postoperative pain control. In this study, we assessed the efficacy of transnasal butorphanol (TB) for pain relief following uvulopalatopharyngoplasty (UPPP) in obstructive sleep apnea (OSA) patients, and compared pain alleviation effect to oral mefenamic acid and intramuscular meperidine (M> or =&M). METHODS: A prospective, randomized, open label study was conducted in a tertiary care sleep center. Twelve OSA patients with full consciousness and at least moderate oropharyngeal pain (pain visual analogue scale [VAS] > or = 4) after UPPP were recruited. They were randomized to receive TB (n = 7) and M&M (n = 5). Oropharyngeal pain was measured by a VAS and the Clinical Global Impression in Severity (CGI-S) and Improvement (CGI-I) at the 12th, 24th, and 72th hours postoperatively. Postoperative pain related morbidities (PRMs) and quality of life in bodily pain (QOL-BP) were also evaluated 72 hours postoperatively. Adverse events incurred by pain treatment were carefully monitored during patients' hospitalizations. RESULTS: No major complication occurred throughout the study. Analysis of clinical measures revealed significantly improved VAS (p = 0.04), CGI-S (p = 0.03), and CGI-I (p = 0.02) in the TB group. However, no significant difference (p > 0.05) in the degree of pain relief was found between the two groups, as denoted by aforementioned three variables, PRMs, and QOL-BP. CONCLUSIONS: Administration of TB can significantly alleviate the wound pain after UPPP in OSA patients. This study also confirmed the safety of TB in patients undergoing oropharyngeal surgery.

Comparison of efficacy of oral drotaverine plus mefenamic acid with paracervical block and with intravenous sedation for pain relief during hysteroscopy and endometrial biopsy.

BACKGROUND: Office hysteroscopy with endometrial biopsy is usually the first investigation for abnormal uterine bleeding and other uterine diseases. AIMS: To evaluate the effect of oral drotaverine with mefenamic acid on pain perception during hysteroscopy and endometrial biopsy and to compare it with that of paracervical block using 1% lignocaine and with that of intravenous sedation using diazepam with pentazocine. SETTINGS AND DESIGN: Outpatient gynecological department and open randomized trial. MATERIALS AND METHODS: One hundred twenty women undergoing hysteroscopy and endometrial biopsy were randomized into 3 groups. Group I received tablet containing drotaverine hydrochloride (80 mg)+mefenamic acid (250 mg), group II received lignocaine paracervically and group III received intravenous diazepam. The intensity of pain during the procedure, 30 and 60 minutes later on visual analog scale (VAS) was assessed. STATISTICAL ANALYSIS: Statistical analysis was performed using Kruskal-Wallis test, with the Bonferroni correction, the t test, and the chi2 test. RESULTS: Groups were similar in age, parity, vaginal birth or relevant medical history. A statistically significant difference in pain scores was noted among the 3 groups during the procedure (group I, 4.13+/-1.28; group II, 5.93+/-1.26; group III, 5.58+/-1.51), (P<0.001); as well as 30 minutes later (group I, 1.78+/-0.89; group II, 2.53+/-0.81; group III, 2.23+/-0.94), (P<0.001) and 60 minutes later (group I, 1.2+/-0.46; group II, 1.98+/-0.83; group III, 1.68+/-0.75), (P<0.001). VAS at different time intervals among the groups was also statistically significant. No adverse effects were observed. CONCLUSIONS: Oral drotaverine with mefenamic acid is effective in women undergoing hysteroscopy and endometrial biopsy.

Pediatric posterior reversible leukoencephalopathy syndrome and NSAID-induced acute tubular interstitial nephritis.

Reversible posterior leukoencephalopathy syndrome is a recently described disorder with typical radiologic findings in the posterior regions of the cerebral hemisphere and cerebellum. The symptoms include headache, nausea, vomiting, visual disturbances, focal neurologic deficits, and seizures. A 10-year-old male was hit on his back, resulting in backache. He was medicated with sodium diclofenate and mefenamic acid. The next day, he had edema and oliguria. By the third day, his blood pressure increased and he began to experience restlessness and worsening mental status. He then complained of headache and visual disturbances and had a seizure. A magnetic resonance imaging scan revealed abnormalities in the posterior regions of the cerebral hemisphere and cerebellum. The patient was treated with antiepileptics and calcium antagonists. His hypertension and seizures were well controlled. On the 22nd day, he was discharged without any neurologic or renal deficits. Reversible posterior leukoencephalopathy syndrome does not occur frequently in childhood, and this is the first case report of reversible posterior leukoencephalopathy syndrome related to nonsteroidal anti-inflammatory drugs. One should consider reversible posterior leukoencephalopathy syndrome as a side effect of nonsteroidal anti-inflammatory drug use in daily medical treatment.

Dendrimers of citric acid and poly (ethylene glycol) as the new drug-delivery agents.

Citric acid-polyethylene glycol-citric acid (CPEGC) triblock dendrimers as biocompatible compounds containing G(1), G(2) and G(3) were applied as the drug-delivery systems. Some of the small size molecules and drugs are trapped with the above-synthesized dendrimers. The guest molecules, which are hydrophobic when trapped into the suitable sites of dendrimers, are becoming soluble in aqueous solution. The quantity of trapped molecules and drugs such as 5-amino salicylic acid (5-ASA), pyridine, mefenamic acid, and diclofenac was measured. The drug/dendrimer complexes remained in room temperature for about 10 months and after this long time they were stable and the drugs were not released. Also, the controlled release of the above-mentioned molecules and drugs in vitro conditions was investigated. The structure definition and controlled release of the molecules and drugs were carried out using different spectroscopy methods.

[Acute renal failure--"a well meant present from a friend"]. / Akutes Nierenversagen--"ein Geschenk einer Freundin".

Acute allergic interstitial nephritis (AIN) due to non-steroidal anti-inflammatory drugs (NSAID) is a well known but rare adverse drug event. Here, we describe the case of a 70 year old woman with recurrent episodes of acute renal failure. A first episode of (AIN) occurred after the intake of mefenaminic acid tablets. A second episode of AIN occurred two years later, this time after transdermal application of diclofenac. Our case illustrates cross-reactivity between NSAIDs and shows that transdermally applied medication can cause systemic adverse events as well. Patients do not mention ointments because they often do not realize that ointments contain active substances, and physicians forget to ask.

Do non-steroidal anti-inflammatory drugs have an effect on gastric cell turnover?

AIM: To study the effect of non-steroidal anti-inflammatory drugs (NSAIDs) on gastric cell turnover using an in vitro immunohistochemical method of bromodeoxyuridine (BrDU) uptake. METHODS: Thirty patients undergoing routine upper gastrointestinal endoscopy were studied. Sixteen had taken NSAIDs daily for more than 3 months and there were 14 age-matched controls. Endoscopic gastric antral biopsies were obtained and stained immediately using the BrDU technique. Cell proliferation was expressed as a labelling index percentage (LI%) defined as the number of BrDU-labelled nuclei in 10 gastric glands, expressed as a percentage of the total cells in the gastric gland. RESULTS: Gastric infection with Helicobacter pylori was excluded in all patients. Of the 16 patients on NSAIDs, four had gastritis, four had erosions or ulceration and eight had a normal examination. Endoscopy was normal in all patients in the control group. The LI% (mean +/- S.E.M.) in the entire NSAID group was 4.09 +/- 0.29 and in the control group 3.57 +/- 0.29. No significant difference was observed. In the NSAID patients with gastritis and erosions or ulceration, the LI% was 4.99 +/- 0.61 and 3.07 +/- 0.32, respectively. There was no significant difference in LI% between the endoscopic subgroups of patients on NSAIDs or between patients on NSAIDs who had normal endoscopy and the control patients. CONCLUSION: These results provide evidence that refutes the hypothesis that the prevalence of NSAID gastropathy is due to an effect on gastric cell turnover.

Local anaesthetic on Filshie clips for pain relief after tubal sterilisation: a randomised double-blind controlled trial.

Pain during tubal sterilisation is thought to be due to either ischaemia or pressure at the site of impact of sterilising devices on the fallopian tubes. We have evaluated the effectiveness of an application of 2% lignocaine gel to Filshie clips to relieve postoperative pain. In a randomised double-blind placebo-controlled study, 80 healthy women undergoing tubal sterilisation under general anaesthesia at the County Hospital, Lincoln, UK, were allocated to be sterilised by Flishie clips covered with 2% lignocaine gel or K-Y gel as placebo. Pelvic pain was assessed, with a 100 mm visual analogue scale, at 1 hour, at hospital discharge, and time of first analgesia or any other time analgesia was demanded. The lignocaine-treated group had significantly longer time to first analgesia, less pain at 1 hour, less nausea and vomiting, and shorter recovery time. Fewer lignocaine-treated patients needed additional analgesia and they required fewer opioids. There was no case of failed sterilisation or adverse reaction to lignocaine. The application of local anaesthetic gel to Filshie clips is a safe, non-invasive, and effective method of relieving postoperative pain during laparoscopic tubal sterilisation.

[Segmental small intestine lesions after taking non-steroidal antirheumatic drugs]. / Segmentale Dünndarmläsionen nach Einnahme nicht-steroidaler antirheumatika.

Over a period of 7 months a 51-year-old diabetic took mefenamine acid (up to 500mg 20 times daily), diclofenac and, more rarely, paracetamol for lumbosacral pain. In addition, dexamethasone (4 mg three times daily) was prescribed later. For 4 weeks he had colicky abdominal pain which then started acutely to radiate into the flanks. Pressure and rebound pain in the left epi- and mesogastrium, as well as the results of biochemical tests, suggested an acute abdomen. Abdominal X-rays, selective contrast examination of the small intestine and computed tomography demonstrated changes within some segments of the jejunum (thickened wall, irregular wall surface). Laparoscopy showed brown discoloration of the loops of the small intestine. In consequence of these findings a 10 cm long segment of the jejunum was resected. Histological examination showed extensive ulcers at the tip of the rugae with granulating inflammation and bifringent foreign bodies with giant-cells. The villi were extensively atrophied, the blood vessel were congested and the submucosa fibrosed. The patient was discharged after 9 days and, no longer taking NSAIDs, has been free of abdominal symptoms.

Tratamiento de la dismenorrea primaria: estudio comparativo de ibuprofen y ácido mefenámico / Treatment of primary dysmenorrhea: comparative study of ibuprofen and mefenamic acid

Se estudio el efecto terapéutico del ácido mefenámico (Grupo A) y del ibuprofen (Grupo B) en el tratamiento de la dismenorrea primaria severa. Se estudiaron 60 pacientes en base doble ciego en 2 grupos de 30 pacientes seleccionadas al azar. El grado inicial del dolor para el Grupo A fue de 8.6 y 8.5 para el primero y segundo ciclo y para el Grupo B de 8.2 en ambos ciclos. El tratamiento se inició en el momento en que se presentó el cólico menstrual y se administró una tableta del medicamento cada 8 horas durante el tiempo que duró el cólico menstrual. La intensidad del cólico menstrual se registró en la escala visual análoga (0 = no dolor, 10 = dolor incapacitante) en el momento del inicio del dolor y a las 2 horas de tomar la primera tableta del medicamento después de registró cada 8 horas antes de tomar la tableta correspondiente. La disminución del dolor se inició después de haber tomado la segunda tableta en ambos grupos siendo progresiva con el uso del medicamento. El número de tabletas tomadas fue en promedio 5.0 y 4.8 para el Grupo A y de 4.3 y 4.2 para el Grupo B. El promedio de la duración del dolor fue para el Grupo A 23.4 y 21 horas y para el Grupo B de 20 y 18.9 horas para el primero y segundo ciclos respectivamente

Analgesia following arthroscopic knee surgery. A controlled study of intra-articular morphine, bupivacaine or both combined.

In a double-blind, randomised controlled trial, we studied 40 patients who received one of four intra-articular injections at the end of arthroscopic surgery. Each group contained ten patients. The patients in Group 1 received normal saline 25 ml; those in Group 2 received bupivacaine 0.25% 25 ml; those in Group 3 received morphine 5 mg in normal saline 25 ml; and those in Group 4 received a combination of bupivacaine 0.5% 12.5 ml and 5 mg of morphine made up to 25 ml with normal saline to produce the same bupivacaine concentration as Group 2. At the time the patient awoke, and 30min, 1hr, 1hr 30min, 2hr, 4hr, 8hr, 12hr, and 24hr postoperatively, pain was assessed using a visual analogue scale. The need for supplementary analgesic agents in the first 24 hours was recorded. All pain scores were significantly lower (P < 0.05) in Groups 2, 3 and 4 compared with the control group with the exception of Group 2 at 24 hours. Pain scores were significantly lower (P < 0.05) for Group 2 compared with Group 3 for the first 90 minutes postoperatively. At 4, 8, 12 and 24 hours postoperatively the pain scores were significantly lower (P < 0.05%) for Group 3 compared with Group 2. Group 4 had the lowest pain scores over the recorded period compared with the other groups. The need for supplemental analgesia was significantly lower (P < 0.05) in the treatment Groups 2, 3 and 4 compared to the control Group 1. There was no significant difference in supplemental analgesic requirements between Groups 2, 3 and 4.(ABSTRACT TRUNCATED AT 250 WORDS)