Mg Of Indomethacin Research Articles

Severe heterotopic ossification after total hip arthroplasty in male patients under 70years of age: effectiveness of prophylactic protocol.

This study aims to evaluate the incidence of clinically significant heterotopic ossification (HO) in primary total hip arthroplasty (THA), comparing outcomes with and without the adoption of an HO prophylactic protocol in male patients under 70years of age. The prophylactic protocol involved the administration of 50mg of Indomethacin twice daily for 3 weeks. HO presence was classified according to the Brooker classification system, considering "severe" clinically significant HO (Brooker grade 3 and 4). Two hundred and seventy-nine patients were included in our study, and an overall HO rate of 68.2% versus a rate of 61.5% was found respectively in patients not subjected and subjected to prophylactic protocol, without significant difference (PR 0.062). However, patients not subjected to the HO prophylactic protocol exhibited a severe HO rate of 22.4% compared to 7.7% in the prophylactic group, with a statistically significant difference (P = 0.008). Our study demonstrated that prophylactic protocol adoption is significantly associated with lower rate of severe HO in male patients under 70years of age. Currently, there are no orthopedic guidelines for the prevention and management of HO after THA, but in the absence of contraindications, the adoption of a prophylactic protocol for HO should always be considered in high-risk patients.

Quantitative analysis of caffeine, ethoxybenzamide, chlorzoxazone, diazepam and indomethacine illegally adulterated in Chinese medical pills

A traditional Chinese medicine, which was brought by a consumer for treating heart disease and uricosuria, was obtained and tested the illegal adulteration with chemical drugs. In the qualitative analysis, two-dimensional TLC, with chloroform:ethanol (9:1,v/v) and ethyl acetate: methanol: ammonia water (8:1:1,v/v) as the solvent systems, established the presence of caffeine, indomethacin, ethoxybenzamide, chlorzoxazone and diazepam in the pills. For quantitative analysis, a reversed-phase HPLC method was established for simultaneous determination of the five chemical drugs. The analysis of the sample extract was performed on a Cosmosil 5C 18-AR column (4.6x150mm) by a linear gradient elution with the mobile phase of 0.05 M KH 2 PO 4-0.1% formic acid buffer and methanol, programmed from 60:40, v/v, to 40:60, v/v, for 30 min, with 30 mim hold and then 60:40, v/v, for the subsequent 15 min, at a flow rate of 0.7 ml/min and with propylparaben as an internal standard. The monitor wavelength was set at 230 nm. System suitability tests showed that the established method was quite suitable for the determination of the adulterants in the pills. By using this method, 30.8mg of caffeine, 71.4 mg of ethoxybenzamide, 35.7 mg of chlorzoxazone, 0.6 mg of diazepam and 9.3 mg of indomethacin, were found in each pill of the sample.

Interventional Endoscopy.

Introduction: Rectal indomethacin and papillary spray of epinephrine have separately shown efficacy for the prevention of post-ERCP pancreatitis (PEP) in randomized controlled trials. We hypothesized that the combination of papillary spray of epinephrine and indomethacin may further reduce PEP over indomethacin alone. Methods: We conducted a comparative effectiveness, multicenter, double-blind, randomized trial comparing rectal indomethacin alone versus a combination of papillary spray of epinephrine and rectal indomethacin for the prevention of PEP in high risk patients. Patients with suspected sphincter of Oddi dysfunction (SOD) type 3 and those who received a pancreatic stent were excluded. Patients were randomized to receive either 100 mg of indomethacin and papillary spray of 20 mL of normal saline (indomethacin alone group) or 100 mg of indomethacin and papillary spray of 20 mL of 0.02% epinephrine (combination group) at the end of ERCP. A Data and Safety Monitoring Board conducted interim analyses with prespecified stopping rules. The primary outcome was the incidence of PEP and the secondary outcome was the severity of PEP, both defined by the consensus criteria. A total of 948 patients (474 in each group) would provide a power of 80% at a 2-sided significance level of 5% to detect a 50% difference in the rates of PEP, assuming PEP rates of 10% and 5%, respectively, for rectal indomethacin and the combination. A two-tailed Fisher's exact test was used to analyze the difference in the proportion of patients with PEP in the indomethacin alone versus the combination group. Results: A total 959 of patients (mean age 52.33±14.96 years; 551 (57.4%) females) were randomized for this trial. The baseline demographic and clinical characteristics were similar between the two groups. Females < 50 years of age (25.4%) and difficult cannulation (84.9%) were the most common patient and procedural risk factors, respectively. Trainees were involved in 24% of the cases. The incidence of PEP was 6.4% in the indomethacin alone group (n=482) compared to 6.7% in the combination group (n=477) (p=0.87). Severe PEP was found in 5 (12%) versus 7 (16%) patients in the indomethacin alone and combination groups, respectively (p=0.88). The overall mortality was 0.6% which was unrelated to the primary outcome. Conclusion: The combination of papillary spray of epinephrine and rectal indomethacin does not reduce the incidence of PEP compared to rectal indomethacin alone in high risk patients.FigureTable: Table. Association of risk factors with the incidence of PEP

Prednisolone, Indomethacin Similarly Effective for Acute Gout

Prednisolone, Indomethacin Similarly Effective for Acute Gout

The role of cyclo-oxygenase-1 in high-salt diet-induced microvascular dysfunction in humans.

Recent studies have shown that some of the deleterious effects of a high-salt (HS) diet are independent of elevated blood pressure and are associated with impaired endothelial function. Increased generation of cyclo-oxygenase (COX-1 and COX-2)-derived vasoconstrictor factors and endothelial activation may contribute to impaired vascular relaxation during HS loading. The present study aimed to assess the regulation of microvascular reactivity and to clarify the role of COX-1 and COX-2 in normotensive subjects on a short-term HS diet. The present study demonstrates the important role of COX-1 derived vasoconstrictor metabolites in regulation of microvascular blood flow during a HS diet. These results help to explain how even short-term HS diets may impact upon microvascular reactivity without changes in blood pressure and suggest that a vasoconstrictor metabolite of COX-1 could play a role in this impaired tissue blood flow. The present study aimed to assess the effect of a 1-week high-salt (HS) diet on the role of cyclo-oxygenases (COX-1 and COX-2) and the vasoconstrictor prostaglandins, thromboxane A2 (TXA2 ) and prostaglandin F2α (PGF2α ), on skin microcirculatory blood flow, as well as to detect its effect on markers of endothelial activation such as soluble cell adhesion molecules. Young women (n=54) were assigned to either the HS diet group (N=30) (∼14gday(-1) NaCl) or low-salt (LS) diet group (N=24) (<2.3gday(-1) NaCl) for 7 days. Post-occlusive reactive hyperaemia (PORH) in the skin microcirculation was assessed by laser Doppler flowmetry. Plasma renin activity, plasma aldosterone, plasma and 24h urine sodium and potassium, plasma concentrations of TXB2 (stable TXA2 metabolite) and PGF2α , soluble cell adhesion molecules and blood pressure were measured before and after the diet protocols. One HS diet group subset received 100mg of indomethacin (non-selective COX-1 and COX-2 inhibitor), and another HS group subset received 200mg of celecoxib (selective COX-2 inhibitor) before repeating laser Doppler flowmetry measurements. Blood pressure was unchanged after the HS diet, although it significantly reduced after the LS diet. Twenty-four hour urinary sodium was increased, and plasma renin activity and plasma aldosterone levels were decreased after the HS diet. The HS diet significantly impaired PORH and increased TXA2 but did not change PGF2α levels. Indomethacin restored microcirculatory blood flow and reduced TXA2 . By contrast, celecoxib decreased TXA2 levels but had no significant effects on blood flow. Restoration of of PORH by indomethacin during a HS diet suggests an important role of COX-1 derived vasoconstrictor metabolites in the regulation of microvascular blood flow during HS intake.

Solidified Reverse Micellar Solution (SRMS)-Based Indomethacin Sustained-Release Tablets: Formulation and &lt;i&gt;In vitro&lt;/i&gt; Evaluation

Purpose: To formulate and evaluate sustained-release indomethacin tablets based on solidified reverse micellar solution (SRMS).Methods: SRMS consisting of mixtures of phospholipid (Phospholipon® 90H) and triglyceride (Softisan® 154) were prepared in the ratios of 1:1, 2:1 and 1:2, respectively. SRMS-based tablets containing 75 mg of indomethacin each were prepared using a validated plastic mould. The physicochemical properties of the tablet formulations were studied. In vitro release study was carried out in simulated intestinal fluid (SIF, pH 7.5).Results: The results showed that the physicochemical properties of the tablet formulations were significantly affected by the composition/ratio of the lipid matrix used (p &lt; 0.05). Tablet hardness ranged from 5.00 ± 0.39 to 5.60 ± 0.36 kgf for tablets formulated with SRMS 1:2 and 2:1 (N3 and N2), respectively. The tablets exhibited friability of &lt; 1 % (p &lt; 0.05). Erosion time in SIF ranged from 124.0 ± 0.5 to 180.0 ± 1.1 min while drug release from the tablets reached a maximum in 8 – 11 h for all thebatches.Conclusion: Indomethacin tablets based on SRMS exhibited good sustained-release properties and can be further developed to achieve once daily administration for improved patient adherence to therapy.Keywords: Solidified reverse micellar solution, Phospholipid, Triglyceride, Indomethacin, Sustained release.

A Randomized Trial of Rectal Indomethacin and Sublingual Nitrates to Prevent Post-ERCP Pancreatitis

Acute pancreatitis is the most common adverse event of endoscopic retrograde cholangiopancreatography (ERCP). Recent data suggest that indomethacin can reduce the risk of post-ERCP pancreatitis (PEP) in high-risk individuals. However, whether the combination of indomethacin and sublingual nitrates is superior to indomethacin alone is unknown. Therefore, we aimed to evaluate the efficacy of rectally administered indomethacin plus sublingual nitrate compared with indomethacin alone to prevent PEP. During a 17-month period, all eligible patients who underwent ERCP were enrolled in this study. We excluded patients who had undergone a prior endoscopic sphincterotomy. In a double-blind controlled randomized trial, patients received a suppository containing 100 mg of indomethacin, plus 5 mg of sublingual nitrate (group A), or a suppository containing 100 mg of indomethacin, plus sublingual placebo (group B), before ERCP. Serum amylase levels and clinically pertinent evaluations were measured in all patients after ERCP. Of the 300 enrolled patients, 150 received indomethacin plus nitrate. Thirty-three patients developed pancreatitis: 10 (6.7%) in group A and 23 (15.3%) in group B (P=0.016, risk ratio=0.39, 95% confidence intervals (CI): 0.18-0.86). More than 80% of the patients were at high risk of developing pancreatitis after ERCP. Absolute risk reduction, relative risk reduction, and number needed to treat for the prevention of PEP were 8.6% (95% CI: 4.7-14.5), 56.2% (95% CI: 50.6-60.8), and 12 (95% CI: 7-22), respectively. Combination of rectal indomethacin and sublingual nitrate given before ERCP was significantly more likely to reduce the incidence of PEP than indomethacin suppository alone. Multicenter trials to confirm these promising findings are needed.

Anti-inflammatory, antinociceptive and ulcerogenic properties of indomethacin tablets based on solidified reverse micellar solution (SRMS)

The aim of the present study was to evaluate in vivo the anti-inflammatory, antinociceptive and ulcerogenic properties of indomethacin tablets based on solidified reverse micellar solution (SRMS). SRMS consisting of mixtures of phospholipid (Phospholipon® 90H) and triglyceride (Softisan® 154) were prepared in the ratios of 1:1, 2:1 and 1:2, respectively. SRMS based tablets containing 75 mg of indomethacin each were prepared using validated plastic mould. The physicochemical properties of the tablet formulations were studied using both official and unofficial tests. Anti-inflammatory, analgesic/antinociceptive and ulcerogenic properties of indomethacin tablets based on SRMS were studied. The results showed that the physicochemical properties of the tablet formulations were significantly affected by the composition/ratio of the lipid matrix used. The softening time in SIF ranged from 53.7 ± 0.5 to 102.6 ± 0.5 min. Results of analgesic/antinociceptive properties showed that indomethacin tablets formulated with the SRMS 1:1 had an increase in pain reaction time at 7 h significantly (p < 0.05) different from the results exhibited by tablets formulated with the lipid matrices, SRMS 1:2 and 2:1 and the reference, which showed a decrease in pain reaction time at 7 h. Indomethacin tablets based on SRMS had good anti-inflammatory properties and also inhibited the ulcerogenicity of indomethacin by 70 to 80%. Therefore, indomethacin tablets based on SRMS could be used for improved oral bioavailability of indomethacin and to enhance patient’s compliance due to inhibition of gastric irritation effect of this drug. Key words: Non steroidal anti-inflammatory drugs (NSAIDS), solidified reverse micellar solutions (SRMS), tablets, ulcerogenicity, antinociception, lipids.

Effect of indomethacin on cerebrovascular reactivity in patients with type 2 diabetes mellitus

AimImpaired cerebral vasoreactivity to endothelium-dependent stimuli were described in type 2 diabetes mellitus (T2DM), but the mechanisms underlying that impairment are still unclear. The aim of this study was to investigate the role of cyclooxygenases’ metabolites in response to acute hypercapnic stimulus in cerebral vessels, in patients with T2DM. MethodsVascular responses in the breath-holding test (BHT) were assessed in the absence/presence of a non-selective, reversible-inhibitor of cyclooxygenases, indomethacin (INDO), by functional transcranial Doppler sonography of the middle cerebral artery (N of patients=50; 33 men and 17 women). The functional hemodynamic parameter mean flow velocity (MFV) was assessed at rest, before and 90min after 100mg of INDO, and during the BHT. Breath holding index (BHI) [(MFV at the end of BHT minus MFV at rest)/MFV at rest)×100/s of breath-holding] was calculated after BHT performed before and 90min after INDO. ResultsMFV at rest significantly decreased after INDO administration compared with a control condition before INDO (at rest before INDO from 49.36±15.09 to 36.72±8.45 after INDO, p<0.001) However, overall cerebral vessel vasoreactivity to hypercapnia, evaluated with BHI, was significantly improved after INDO administration compared with the BHI before INDO administration (from 0.68±0.4 to 1.27±0.42, p<0.001). ConclusionsThe improvement in cerebral vasoreactivity in response to BHT after INDO administration suggests that the production of a vasoconstrictor metabolite of cyclooxygenase in diabetic patients was reduced by indomethacin consumption.

Exacerbation of Obstructive Sleep Apnea by Oral Indomethacin

Patients with obstructive sleep apnea (OSA) are predisposed to instability in central ventilatory control during sleep. Increased instability, as reflected in an enhanced expired volume in per unit time loop gain, has been associated with a greater predisposition to upper airway collapse. Here, in an otherwise healthy patient with untreated mild OSA, we describe the further exacerbation of OSA after oral indomethacin administration. The subject was a control subject in part of a study to investigate the effects of altering cerebral blood flow (CBF) on ventilatory responses and sleep. He was administered either placebo or 100 mg of indomethacin orally with 20 mL of antacid 2.5 h before sleep on different days. He was studied overnight by polysomnography, arterial blood gases, and transcranial Doppler ultrasound. Administration of 100 mg of oral indomethacin prior to sleep resulted in an almost doubling of the apnea-hypopnea index (14 to 24/h), compared with placebo. This was due to an increase in apneas, rather than hypopneas. Following the indomethacin, changes in arterial blood gases were unremarkable, but both CBF as indexed using transcranial Doppler ultrasound and CBF reactivity to a steady-state change in CO(2) (CBF-CO(2)) reactivity were reduced, and the ventilatory response to CO(2) was elevated. CBF was also further reduced during nonrapid eye movement sleep following the indomethacin when compared with the control night. Indomethacin-induced reductions in CBF and CBF-CO(2) reactivity and related increases in ventilatory instability may lead to a greater predisposition to upper airway collapse and related apnea; these factors may partly explain the exacerbation of OSA.

Combination of indomethacin and statin compared with indomethacin and placebo in patients with a first episode of acute pericarditis: preliminary findings

The aim of the present study was to evaluate the safety and efficacy of the combination of indomethacin and statin compared with indomethacin plus placebo in patients with a first episode of pericarditis. A total of 55 consecutive patients with acute pericarditis were randomized in a double-blind manner into two groups: group 1 (statin group) was treated with 150 mg of indomethacin plus 10 mg of rosuvastatin, and group 2 (placebo group) was treated with 150 mg of indomethacin plus placebo. Both groups received treatment up to the normalization of inflammation markers and for the following week. Clinical and laboratory assessments [white cell count, ESR (erythrocyte sedimentation rate) and CRP (C-reactive protein), troponin I, creatine kinase and brain natriuretic peptide plasma levels], ECG and echocardiogram were performed at baseline and daily up to discharge. All of the patients were followed as outpatients for 3 months to evaluate any recurrence of pericarditis. The two groups were similar in age, sex and laboratory parameters [group 1 (the statin group), n=28 patients; gender, 18 male and ten female; and age, 29.5+/-5.7 years; group 2 (placebo group), n=27 patients; gender, 16 male/11 female; and age, 29.2+/-4.8 years]. The statin group, when compared with the placebo group, had a significantly faster reduction in CRP values (5.0+/-1.0 compared with 6.0+/-2.0 days respectively; P=0.022), ST segment normalization (3.5+/-1.0 compared with 4.5+/-1.0 days respectively; P=0.001), pericardial effusion (4.5+/-1.0 compared with 5.5+/-1.0 days respectively; P=0.001) and ESR (5.0+/-1 compared with 6.0+/-2 days respectively; P=0.022). Our results show that the combination of statin and indomethacin treatment in patients with acute pericarditis is feasible, with a significant reduction in inflammatory markers and a favourable trend in hospitalization time (5.5+/-2.0 compared with 6.5+/-2.0 days respectively; P=0.069). However, these preliminary findings require further studies in a larger sample of patients.

Judge, jury and executioner: the auto-regulation of luteal function

Experiments were conducted to further our understanding of the cellular and molecular mechanisms that regulate luteal function in ewes. Inhibition of protein kinase A (PKA) reduced (P < 0.05) secretion of progesterone from both small and large steroidogenic luteal cells. In addition, the relative phosphorylation state of steriodogenic acute regulatory protein (StAR) was more than twice as high (P < 0.05) in large vs small luteal cells. Large steroidogenic luteal cells appear to contain constitutively active PKA and increased concentrations of phosphorylated StAR which play a role in the increased basal rate of secretion of progesterone. To determine if intraluteal secretion of prostaglandin (PG) F2alpha was required for luteolysis, ewes on day 10 of the estrous cycle received intraluteal implants of a biodegradable polymer containing 0, 1 or 10 mg of indomethacin, to prevent intraluteal synthesis of PGF2alpha. On day 18, luteal weights in ewes receiving 1 mg of indomethacin were greater (P < 0.05) than controls and those receiving 10 mg were greater (P < 0.05) than either of the other two groups. Concentrations of progesterone in serum were also increased (P < 0.05) from days 13 to 16 of the estrous cycle in ewes receiving 10 mg of indomethacin. Although not required for decreased production of progesterone at the end of the cycle, intraluteal secretion of PGF2alpha appears to be required for normal luteolysis. To ascertain if oxytocin mediates the indirect effects of PGF2alpha on small luteal cells, the effects of 0, 0.1, 1 or 10 mM oxytocin on intracellular concentrations of calcium were quantified. There was a dose-dependent increase (P < 0.05) in the number of small luteal cells responding to oxytocin. Thus, oxytocin induces increased calcium levels and perhaps apoptotic cell death in small luteal cells. Concentrations of progesterone, similar to those present in corpora lutea (approximately 30 microg/g), prevented the increased intracellular concentrations of calcium (P < 0.05) stimulated by oxytocin in small cells. In large luteal cells the response to progesterone was variable. There was no consistent effect of high quantities of estradiol, testosterone or cortisol in either cell type. It was concluded that normal luteal concentrations of progesterone prevent the oxytocin and perhaps the PGF2alpha-induced increase in the number of small and large luteal cells which respond to these hormones with increased intracellular concentrations of calcium. In summary, large ovine luteal cells produce high basal levels of progesterone, at least in part, due to a constituitively active form of PKA and an enhanced phosphorylation state of StAR. During luteolysis PGF2alpha of uterine origin reduces the secretion of progesterone from the corpus luteum, but intraluteal production of PGF2alpha is required for normal luteolysis. Binding of PGF2alpha to receptors on large luteal cells stimulates the secretion of oxytocin which appears to activate PKC and may also inhibit steroidogenesis in small luteal cells. PGF2alpha also activates COX-2 in large luteal cells which leads to secretion of PGF2alpha. Once intraluteal concentrations of progesterone have decreased, oxytocin binding to its receptors on small luteal cells also results in increased levels of intracellular calcium and presumably apoptosis. Increased secretion of PGF2alpha from large luteal cells activates calcium channels which likely results in apoptotic death of this cell type.

Chemoinformetrical Evaluation of Dissolution Property of Indomethacin Tablets by Near-Infrared Spectroscopy

Purpose: The purpose of this study was to use near-infrared spectrometry (NIR) with chemoinformetrics to predict the change of dissolution properties in indomethacin (IMC) tablets during the manufacturing process. A comparative evaluation of the dissolution properties of the tablets was performed by the diffused reflectance (DRNIR) and transmittance (TNIR) NIR spectroscopic methods. Methods: Various kinds of IMC tablets (200 mg) were obtained from a powder (20mg of IMC, 18mg of microcrystalline cellulose, 160mg of lactose, and 2mg of magnesium stearate) under various compression pressures (60–398 MPa). Dissolution tests were performed in phosphate buffer, and the time required for 75% dissolution (T75) and mean dissolution time (MDT) were calculated. DRNIR and TNIR spectra were recorded, and the both NIR spectra used to establish a calibration model for predicting the dissolution properties by principal component regression analysis (PCR). Results: The T75 and MDT increased as the compression pressure increased, since tablet porosity decreased with increasing pressure. Intensity of the DRNIR spectra of the compressed tablets decreased as the compression pressure increased. However, the intensity of TNIR spectra increased along with the pressure. The calibration models used to evaluate the dissolution properties of tablets were established by using PCR based on both DRNIR and TNIR spectra of the tablets. The multiple correlation coefficients of the relationship between the actual and predictive T75 by the DRNIR and TNIR methods were 0.831 and 0.962, respectively. Conclusion: It is possible to predict the dissolution properties of pharmaceutical preparations using both DRNIR and TNIR chemoinformetric methods. The TNIR method was more accurate for predictions of the dissolution behavior of tablets than the DRNIR method.

Surgically treated acetabular fractures via a single posterior approach with a follow-up of 2–10 years

The results of operative treatment of acetabular fractures as well as its role in the occurrence of post-traumatic osteoarthritis (OA) are presented. From 1990 to 2000, 50 patients (32 male and 18 female), aging from 18 to 71 years (mean: 37.8 years) underwent an open reduction and internal fixation of their displaced acetabular fracture. They were reviewed at a mean of 5.8 years (2-10 years). A typical Kocher-Langebeck approach was selected in all the patients and in 14 cases a trochanteric osteotomy was added to enhance exposure. The fractures were classified according to the Letournel-Judet classification. The aim of the operation was the anatomic reduction and stable fixation of the fracture with less than 2mm residual displacement, which was achieved in 39 of 50 cases. Post-operative protocol included low-molecular-weight heparin (LWMH) as antithrombotic prophylaxis and 75 mg of indomethacin against heterotopic ossification (HO). At the final follow-up, the patients were evaluated clinically according to D'Aubigne-Postel scoring system and radiologically based on the criteria described by Matta. The clinical results were excellent in 20 patients, good in 18, fair in 5 and poor in 7. The radiological results were excellent in 20 patients, good in 16, fair in 5 and poor in 9. Early post-operative complications included 2 peroneal nerve palsies and 3 wound infections and late complications included 1 patient with avascular necrosis of the femoral head (ANFH), 5 patients with grade III and IV heterotopic ossification according to Brooker classification and 12 patients with post-traumatic osteoarthritis of the hip joint. Although the rates of early and late complications were relatively common, the functional outcome was satisfactory in most of the cases and comparable with other larger series. We concluded that operative treatment of most of the displaced acetabular fractures--except of isolated anterior column or/and anterior wall - could be attempted via a single posterior approach, leading to good to excellent results in the majority of the cases.

Prevention of heterotopic ossification in high-risk patients with total hip arthroplasty: the experience of a combined therapeutic protocol

The combination of radiotherapy and indomethacin for the prevention of heterotopic ossification (HO) in high-risk patients undergoing total hip arthroplasty (THA) has not been reported. The aim of the present study was to present the experience of our department with this combined therapeutic protocol. Fifty-four patients who underwent THA received a single dose of 7 Gy of postoperative radiotherapy and 75 mg of indomethacin for 15 days. Patients were analyzed for clinical and radiographical evidence of HO development at 1 year postoperatively. The overall radiographical incidence of HO was 20.4% (95% CI 10.6-33.5%), while only 1 patient with clinically significant HO was seen. Patients with secondary arthritis due to congenital hip disease had a statistically significantly higher incidence of HO compared with those with osteoarthrosis. The clinical assessment with the Merle d'Aubigné score showed that patients with radiographic documentation of HO had a lower mean score compared with those with no evidence of HO. No treatment-related side effects were seen. Combined radiotherapy and indomethacin was effective in preventing heterotopic ossification after total hip arthroplasty. The evaluation of this efficacy compared with radiotherapy or NSAIDs alone should be the future target of larger randomized designs.

Indomethacin effect on implantation rates in oocyte recipients

Implantation failure is the main limiting factor for success of IVF. Even when transfer techniques are carried out extremely carefully, embryo transfer may produce an endometrial and cervical reaction that may result in an inflammatory response and impaired implantation. There are no formal specifications on the use of indomethacin in reproductive cycles and there are no studies published in the scientific literature on its effect on embryo implantation. Oocyte donation is the best model to evaluate the determinants of implantation. The aim of this study is to evaluate the potential benefit of indomethacin administered at embryo transfer. A randomized pilot trial of 136 oocyte recipients was carried out. Seventy-two women received standard specifications plus 100 mg of indomethacin rectally given as three doses every 12 h starting on the night prior to transfer. Positive HCG (>= 6 mUI/ml) occurred in 59.7% of treated women and in 59.4% of women in the control group. Implantation rates were 27.8% in the indomethacin group and 26.4% in the controls. The indomenthacin group did not show significantly higher implantation rates. A larger study exploring alternative treatment protocols might be appropriate.

Acute renal failure associated with an accidental overdose of colchicine

A 47-year-old man with a history of polyarticular gout was admitted to the nephrology service because of severe renal insufficiency (creatinine 6.25 mg/dl). Three days before admission he had a pain crisis in his knees and ankles and self-administered 20 x 1 mg granules of colchicine p.o. over a period of 4 - 5 hours together with six suppositories each containing 100 mg of indomethacin. The patient began vomiting within 24 hours, experienced diarrhea which persisted for three days and then came to the hospital. The patient reported oliguria during the preceding 24 hours. In hospital, attempts to correct water and electrolyte balance were initiated. The patient became stabilized hemo-dynamically, the diarrhea disappeared within 24 hours, diuresis resumed and the renal function progressively improved. Leukopenia and thrombopenia were diagnosed, the transaminases increased: AST = 79 U/l, ALT = 132 U/l on the eighth day after taking the colchicine. The serology for hepatitis A, B, C and HIV viruses was negative; the serology for CMV and VEB revealed a previous infection. After being discharged from hospital 11 days after admission, the patient presented with the following parameters: hematocrit 39%, leukocytes 5,920/microl (3 470 neutrophils), prothrombin time 13 seconds, urea 44 mg/dl, creatinine 1.29 mg/dl, AST 16 U/l and ALT 35 U/l.The patient mistakenly ingested 20 mg ofcolchicine p.o. (0.22 mg/kg). The intoxication was associated with gastroenterocolitis, dehydration and renal failure during the first three days after ingestion. The patient also developed leukopenia, thrombopenia and mild hepatocellular injury. Renal failure due to colchicine intoxication is due to various factors such as depletion of volume/hypotension, rhabdomyolysis and multiorgan failure. In this case, the hypovolemia was probably the fundamental cause of the acute renal insufficiency as demonstrated by the quick recovery after administering fluids. It is possible that indomethacin may have enhanced the toxic effect of colchicine on the kidneys and bone marrow. Some colchicine intoxications, as in this case, are caused by an error in interpreting the dose for treating an acute attack of gout. A way to prevent these errors would be to use a low-dose treatment protocol.

Tympanic Displacement Analysis in Healthy Volunteers after Indomethacin Administration

The aim of this study was to investigate whether a tympanic displacement analyser could detect decreases in cerebral blood flow and intracranial pressure after administration of indomethacin in healthy volunteers. In a double-blind crossover study involving 14 healthy volunteers all subjects first underwent a test-retest evaluation to investigate reproducibility followed by tests performed in sitting and supine positions to confirm intracranial-cochlear pressure transfer. In two further sessions tests were performed before and 90 min after subjects were blindly administered a suppository containing either 100 mg of indomethacin or placebo. It was found that tympanic membrane analysis performed 90 min after administration of such a suppository did not mirror the induced reduction in cerebral blood flow after administration of active drug. After administration of indomethacin eight of the subjects experienced discomfort and dizziness; after placebo none experienced subjective symptoms. After administration of indomethacin a statistically significant decrease in heart rate was demonstrated. The exponential form of the intracranial pressure-volume curve may explain why a decrease in intracranial pressure was not detected using the tympanic membrane displacement method, because the measurements were made in subjects with normal intracranial pressure. More significant findings may be found in patients with elevated intracranial pressure.

AMMONIUM MOLYBDATE AS A SPECTROPHOTOMETRIC REAGENT FOR THE DETERMINATION OF INDOMETHACIN IN PURE AND PHARMACEUTICAL PREPARATIONS

ABSTRACT Indomethacin reacts with ammonium molybdate in concentrated hydrochloric acid to give a violet colour after heating for 5 min at 100°C having maximum absorbance at 550 nm. The reaction is selective for indomethacin with 0.01 mg/10 mL as visual limit of identification and provides a basis for a new spectrophotometric determination. The reaction obeys Beer's Law from 0.01 mg to 3 mg/10 mL of indomethacin and the relative standard deviation for 0.01 mg of indomethacin is 0.71%. The quantitative assessment of common interferences and tolerable amount of other drugs is also studied.

Tympanic Displacement Analysis in Healthy Volunteers after Indomethacin Administration

The aim of this study was to investigate whether a tympanic displacement analyser could detect decreases in cerebral blood flow and intracranial pressure after administration of indomethacin in healthy volunteers. In a double-blind crossover study involving 14 healthy volunteers all subjects first underwent a test-retest evaluation to investigate reproducibility followed by tests performed in sitting and supine positions to confirm intracranial-cochlear pressure transfer. In two further sessions tests were performed before and 90 min after subjects were blindly administered a suppository containing either 100 mg of indomethacin or placebo. It was found that tympanic membrane analysis performed 90 min after administration of such a suppository did not mirror the induced reduction in cerebral blood flow after administration of active drug. After administration of indomethacin eight of the subjects experienced discomfort and dizziness; after placebo none experienced subjective symptoms. After administration of indomethacin a statistically significant decrease in heart rate was demonstrated. The exponential form of the intracranial pressure-volume curve may explain why a decrease in intracranial pressure was not detected using the tympanic membrane displacement method, because the measurements were made in subjects with normal intracranial pressure. More significant findings may be found in patients with elevated intracranial pressure.