Long-term use and tolerability of cyclooxygenase-2 inhibitors in patients with analgesic intolerance.

BACKGROUND: Cyclooxygenase-2 (COX-2) inhibitors are reported to be well tolerated in patients with analgesic intolerance (AI). However, limited data are available about the long-term tolerability of these drugs. OBJECTIVE: To determine the long-term tolerability of COX-2 inhibitors in patients with Al. METHODS: Patients with AI who previously underwent single-masked, placebo-controlled oral provocation tests and were found to tolerate nimesulide, meloxicam, rofecoxib, or celecoxib were interviewed regarding the long-term use and tolerability of these drugs. RESULTS: Of 87 patients, 61 (70%) had used the recommended COX-2 inhibitor(s). Of the 61 users, 54 (89%) tolerated the drug(s) well and 7 (11%) reported adverse events. Three patients reporting adverse events were rechallenged with the responsible COX-2 inhibitor, and their results were found to be negative. CONCLUSIONS: Long-term use of COX-2 inhibitors was tolerated well by most patients with AI, and placebo-controlled oral provocation tests, as a single test, seemed to predict tolerability. Furthermore, self-reported positive reactions in the long-term should also be confirmed with rechallenge tests for definite diagnosis.     

Brainstem evaluation in children with primary nocturnal enuresis

We investigated the brainstem integrity in children with primary nocturnal enuresis (PNE) using auditory brainstem responses (ABR), blink reflex and exteroceptive suppression of the masseter muscle. We examined 23 children with PNE (16 male, 7 female; mean age: 10.4 years) and 19 control subjects (11 male, 8 female; mean age: 11.8 years). ABR parameters such as wave latencies, amplitudes and interpeak latencies and blink reflex parameters such as R1 and R2 amplitude and latencies were not significantly different between the 2 groups. Although S2 parameters of the exteroceptive suppression of the masseter muscle were easily and completely obtained from the control subjects, in the PNE group S2 onset latency and duration were not recorded in 26% of the study children (n = 6) (P = 0.01). S2 duration time was significantly lowered in the enuretic group (left side: P = 0.001 and right side: P = 0.003). S2 duration time changes in the enuretic group supports a possible brainstem dysfunction in children with PNE.     

Determination of allelic deletion of multiple endocrine neoplasm type 1 (MEN1) gene in acute myeloid leukemia (AML) by application of FISH-TSA technique

We have used the single and dual color fluorescence in situ hybridization (FISH) technique combined with a new detection system, tyramide signal amplification (TSA), by using the multiple endocrine neoplasm type 1 (MEN1) gene and chromosome 11 specific alpha satellite DNA probes for the study of the allelic deletion of the MEN1 gene. The MEN1 gene is a new tumor suppressor gene and has been recently cloned on chromosome 11q13. FISH combined with the TSA detection system was performed on bone marrow interphase nuclei of 22 patients with acute myeloid leukemia (AML). The FISH-TSA analysis revealed the mono allelic deletion of the MEN1 gene in 4 out of 22 patients (18.18%), 2 of 9 AML-M2 patients (22.2%), 1 of 6 AML-M4 patients (16.6%), and 1 of 4 AML-M5 patients (25.0%). Our study indicates that allelic deletion of the MEN1 gene is not a major cause or a primary event in tumorigenesis of AML, although the long arm (q13 region) of chromosome 11 involves a chromosomal rearrangement in AML.     

New antimicrobial agents for the treatment of Gram-positive bacterial infections.

Since the 1970s, resistance to antimicrobial agents has become an escalating problem. In the last 25 years, treatment of infections caused by Gram-positive bacteria has been more problematical than ever, with infections being caused by multidrug-resistant organisms, particularly methicillin-resistant staphylococci, penicillin- and erythromycin-resistant pneumococci, and vancomycin-resistant enterococci. There is a continuing effort in the pharmaceutical industry to develop new antimicrobial agents for the treatment of resistant infections. Linezolid, quinupristin-dalfopristin, daptomycin, tigecyline, new glycopeptides and ceftobiprole are the main agents recently introduced or under clinical development. This review summarises their major properties, the results of recent studies with these agents, and future treatment possibilities.     

In vitro and in vivo comparison of three MR measurement methods for calculating vascular shear stress in the internal carotid artery

BACKGROUND AND PURPOSE: Vascular abnormalities, such as atherosclerosis and the growth and rupture of cerebral aneurysms, result from a derangement in tissue metabolism and injury that are, in part, regulated by hemodynamic stress. The purpose of this study was to establish the feasibility and accuracy of determining wall shear rate in the internal carotid artery from phase-contrast MR data. METHODS: Three algorithms were used to generate shear rate estimates from both ungated and cardiac-gated 2D phase-contrast data. These algorithms were linear extrapolation (LE), linear estimation with correction for wall position (LE*), and quadratic extrapolation (QE). In vitro experiments were conducted by using a phantom under conditions of both nonpulsatile and pulsatile flow. The findings from five healthy volunteers were also studied. MR imaging-derived shear rates were compared with values calculated by solving the fluid flow equations. RESULTS: Findings of in vitro constant-flow experiments indicated that at one or two excitations, QE has the advantage of good accuracy and low variance. Results of in vitro pulsatile flow experiments showed that neither LE* nor QE differed significantly from the predicted value of wall shear stress, despite errors of 17% and 22%, respectively. In vivo data showed that QE did not differ significantly from the predicted value, whereas LE and LE* did. The percentages of errors for QE, LE, and LE* in vivo measurements were 98.5%, 28.5%, and 36.1%, respectively. The average residual of QE was low because the residuals were both above and below baseline whereas, on average, LE* tended to be a more biased overestimator of the shear rate in volunteers. The average and peak wall shear force in five volunteers was approximately 8.10 dyne/cm2 and 13.2 dyne/cm2, respectively. CONCLUSION: Our findings show that LE consistently underestimates the shear rate. Although LE* and QE may be used to estimate shear rate, errors of up to 36% should be expected because of variance above and below the true value for individual measurements.     

Ocular toxicity of intravitreal clarithromycin.

OBJECTIVE: To investigate the ocular toxicity and clearance of intravitreal clarithromycin lactobionate (Klaricid) and to determine the highest nontoxic dose. MATERIALS AND METHODS: To evaluate toxicity, 24 New Zealand white rabbits were divided into six groups (four rabbits each). Rabbits were examined preoperatively and electroretinography (ERG) was performed. The left eyes of the animals served as controls and received intravitreal injection of 0.1 mL sterile water. Klaricid (0.1 mL) was injected into the midvitreous cavity of the right eyes at concentrations of 25 microg, 250 microg, 500 microg, 1.0 mg, 2.0 mg, and 4.0 mg/0.1 mL. The animals were followed up to 15 days postinjection by clinical examination and ERG. The animals were killed and the eyes were enucleated and processed for light microscopy. Ten New Zealand rabbits were used for the vitreous clearance study as drug test rabbits and two additional rabbits were used to generate control retina and vitreous. The highest nontoxic dose (1 mg) was injected into the vitreous and the concentration of clarithromycin in the vitreous was determined using high-performance liquid chromatography at various time intervals after injection. RESULTS: Cataract occurred after intravitreal doses of 2.0 and 4.0 mg. Electroretinography showed decreasing b-wave amplitude with both dark- and light-adapted stimulus in the 4.0-mg group; it was normal in other groups. Histopathologic sections showed localized retinal necrosis and disorganization with the 2.0 and 4.0 mg dosage. No histologic changes were found in the other groups. The half-life of intravitreal clarithromycin was found to be 2 hours. No metabolites of clarithromycin were observed in the vitreous samples. CONCLUSION: Intravitreal clarithromycin lactobionate is nontoxic to rabbit eyes up to a dose of 1.0 mg. Because of its broad-spectrum antibiotic effect and appropriate half-life in the vitreous, it may be a good choice for intravitreal treatment of susceptible organisms.     

The effect on the middle-ear cavity of an absorbable gelatine sponge alone and with corticosteroids

The objectives of this study were to establish whether there is an obvious difference between intact mucosa and abraded mucosa of the middle-ear cavity in respect to the potential side effects from the application of absorbable gelatine sponge (Gelfoam) and to investigate if Gelfoam combined with corticosteroid ointment (cortimycine, sterile 1% hydrocortisone acetate) can reduce the occurrence of these effects. Twenty Albino rats were used in the study. These animals were divided into four groups, with ten ears in each group. In group A, the middle-ear mucosa was kept intact, and Gelfoam was inserted into the middle-ear cavity. In group B, the middle-ear mucosa was abraded, and Gelfoam was inserted. In group C, Gelfoam with corticosteroid was implanted over the intact mucosa, and in group D, the mucosa was abraded prior to the insertion of Gelfoam with corticosteroid. The changes were evaluated 8 weeks postoperatively. In group A, there was a minimal increase in fibroblastic activity, vascular proliferation with mild to moderate fibrosis and all but two tympanic membranes were perfectly normal. However, in group B, we encountered a significant increase in fibroblastic activity, vascular proliferation and fibrosis, and we observed that all tympanic membranes were moderately to severely thickened. These histopathologic changes related to Gelfoam were noted to be decreased in group C and especially in group D. As previously reported in the literature, Gelfoam was found to promote the formation of connective tissue in the middle-ear cavity regardless of the status of the mucosa. The unwanted effects of this material may be decreased if it is combined with corticosteroids in the middle-ear cavity.     

Diagnostic power of the vaginal washing-fluid prolactin assay as an alternative method for the diagnosis of premature rupture of membranes.

OBJECTIVE: The purpose of this study was to determine the reliability of the vaginal washing-fluid prolactin assay for the diagnosis of premature rupture of membranes (PROM) and to determine a diagnostic cut-off value. STUDY DESIGN: Seventy pregnant women between 11 and 40 weeks of gestation who were admitted with vaginal fluid leakage were included in the study group, and were then further subdivided into two subgroups according to amniotic fluid pooling and nitrazine paper test results. Group 1 was the 'confirmed PROM group', positive for both pooling and nitrazine (38 patients). Group 2 was the 'suspected but unconfirmed PROM group' which had possible pooling and/or nitrazine (32 patients). Seventy pregnant women between 11 and 40 weeks of gestation without any complaint and complication were included in the control group (group 3). All patients underwent vaginal washing-fluid sampling and prolactin level determination. For the statistical analysis one-way analysis of variance, Tukey multiple comparison test, chi2 test and receiver operating characteristic (ROC) curve analysis were used. RESULTS: Geometric mean values of vaginal washing-fluid prolactin levels were 616.59 microIU/ml for group 1, 23.98 microIU/ml for group 2 and 10 microIU/ml for group 3 (p < 0.0001). The optimal diagnostic cut-off value was found to be 30 microIU/ml with 95% sensitivity, 78% specificity, 84% positive predictive value, 93% negative predictive value, 87% accuracy and 11.30 relative risk. CONCLUSIONS: We recommend vaginal washing-fluid prolactin level determination as an alternative diagnostic method for PROM.