Identifying at diagnosis the vestibular schwannomas at low risk of growth in a long-term retrospective cohort.

OBJECTIVES: Identification at time of diagnosis of those vestibular schwannomas that will not grow. DESIGN: Retrospective cohort study of consecutive patients diagnosed with a sporadic vestibular schwannoma that were entered in the wait-and-scan protocol. SETTING: Academic referral centre. PARTICIPANTS: The study group contained 155 patients with a sporadic vestibular schwannoma first seen in the full 8-year period 2000-2007: continual wait-and-scan (n = 89) and initial wait-and-scan until intervention (n = 66). MAIN OUTCOME MEASURES: Tumour growth, defined as more than 2 mm linear difference in any plane between the diagnostic MRI-scan and the last available scan, was related to clinical parameters at diagnosis: localisation of the tumour (solely intracanalicular versus cisternal extension), sudden sensorineural hearing loss, sensorineural hearing loss longer than 2 years and vertigo/instability. RESULTS: Hearing loss longer than 2 years and an entirely intracanalicular localisation were associated with no tumour growth by univariate and multivariate Cox analysis. Combining both factors at time of diagnosis resulted in a group with low risk of growth (n = 36, median follow-up of 6.2 years) with a Hazard Ratio for growth of 0.37 (95% CI, 0.19-0.69). This subgroup is about 25% of the wait-and-scan population. Thirty-one percent showed growth, while in the remaining higher risk group of 119 patients 62% showed growth. For the growing schwannomas, the median time for growth becoming manifest is 1.9 years after diagnostic MRI. CONCLUSIONS: In this study on vestibular schwannoma patients that start in a wait-and-scan protocol, about a quarter may be set apart having a low risk for growth. These patients at diagnosis combine a history of hearing loss longer than 2 years and a fully intracanalicular schwannoma. They seem to be not needed yearly MRI checks.

Primary hyperparathyroidism: role of the preoperative oral calcium loading test in the differential diagnosis between adenoma and hyperplasia.

Whereas the sensitivity of the membrane calcium receptors is decreased in parathyroid adenoma, extracellular calcium may reduce parathyroid hormone (PTH) secretion through the protein kinase C pathway in parathyroid hyperplasia. The aim of this study was to determine the role of a preoperative oral calcium loading test in the differential diagnosis between adenoma and hyperplasia. Twenty-two subjects with adenoma (group A, age +/- standard error 56 +/-2 years, female/male 15/7), 10 individuals with hyperplasia (group H, age 54 +/-3, female/male 8/2), and 32 age and gender pair-matched controls (group C) underwent the test. Calcium and PTH were measured before and 60, 120, and 180 min after oral administration of 1 g of calcium (as gluconolactate). Product P was defined as minimal PTH concentration (pg/mL) x maximal calcium concentration (mg/dL) during the test. Ratio R was defined as relative PTH decline/relative calcium increase. The PTH decline during the test in group H was comparable to that of the controls. PTH decline <30%, Product P > 1,100, and Ratio R < 4 diagnosed adenoma with specificity of 100%, 90%, and 100%, respectively. PTH decline >60% diagnosed hyperplasia with specificity of 100%. The total accuracy of the test (65%) was comparable to that of technetium-99 m sestamibi scintigraphy (66%) and better than that of ultrasonography (58%). The test may discriminate patients with sporadic diffuse hyperplasia from individuals with solitary adenoma in cases of primary hyperparathyroidism with an indication for surgery.

Fibrin glue treatment for simple and complex anal fistulas.

BACKGROUND/AIMS: Surgical management of anal fistulas is associated with considerable morbidity, mainly related to anal sphincter injury. However, treatment with fibrin glue is a safe and simple method associated with less discomfort and complications. A prospective trial was conducted at our institute to evaluate the use of fibrin glue (Tissucol, Baxter, The Netherlands) for simple and complex anal fistulas. METHODOLOGY: From November 2001 until March 2004, 34 patients (22 male, 12 female, median age 40 years) were treated with Tissucol. Twenty-three (67%) fistulas were classified as simple (subcutaneous, intersphincteric and transsphincteric) and 11 (33%) as complex (suprasphincteric, extrasphincteric and/or associated with Crohn's disease, ulcerative colitis or HIV). RESULTS: Twenty-six patients were treated once, 5 patients were treated twice, 2 patients were treated 3 times and 1 patient underwent 4 Tissucol treatments. After a median follow-up of 7 months, 13 of 23 simple fistulas (56%) and 6 out of 11 complex fistulas (54%) healed, accounting for an overall closure rate of 55%. Complications occurred in two patients, who both developed a perineal abscess after glue instillation. CONCLUSIONS: Fibrin glue treatment is safe and effective in 55% of the patients with anal fistulas. It is a good alternative to conventional surgery.

Development and validation of a rapid HPLC method for the determination of oseltamivir phosphate in Tamiflu and generic versions.

Oseltamivir phosphate (OP) is an antiviral drug that is used in the treatment and prophylaxis of both influenza A and influenza B. It is effective against all known influenza viruses than can infect humans, including pandemic influenza viruses and may be the most appropriate antiviral option against avian influenza caused by H5N1 virus. Tamiflu, the registered trademark used under exclusive license by Roche laboratories with OP as active pharmaceutical ingredient, is considered the best treatment for the bird flu disease. A simple, selective, linear, accurate and precise HPLC method was developed and validated for rapid assay of OP aimed to the quality control of Tamiflu capsules and generic versions. Isocratic elution at a flow rate of 1.2 mL/min was employed on a Zorbax CN column (150 mm x 4.6mm; 5 microm) at ambient temperature. The mobile phase consisted of methanol and 0.04 M formic acid pH 3.0 (50:50, v/v). The UV detection wavelength was 226 nm and 20 microL of sample was injected. Sotalol hydrochloride was used as the internal standard (IS). The retention times for OP and IS were 3.40 and 2.25 min, respectively. The method was successfully applied to commercial pharmaceuticals, Tamiflu and generic versions. The proposed method could be applicable for routine analysis of OP and monitoring of the quality of marketed drugs as possibly counterfeit Tamiflu.

Determination of pKa values of 2-amino-2-oxazolines by capillary electrophoresis.

The dissociation constants of new 2-amino-2-oxazolines were determined by capillary electrophoresis (CE) as a new technique. A method based on a linear model has been used in the CE determination. A series of eight 2-amino-2-oxazolines are investigated to determine their ionization constant. Among them, three new oxazolines synthesized are presented. The Ka values were obtained from the plots of reciprocal effective mobility against inverse concentrations of protons. The potentiometric method (PM) was performed as a comparative method. No significant differences were observed between the determined dissociation constants using both methods. Thus, the pKa values have been found to vary between 8.55 and 8.68.

Spectrophotometric, spectrofluorimetric, HPLC and CZE determination of mirtazapine in pharmaceutical tablets.

Four analytical methods have been developed for the quality control of tablets containing mirtazapine: spectrophotometry, spectrofluorimetry, high performance liquid chromatography (HPLC) and capillary zone electrophoresis (CZE). All the methods only require a simple extraction procedure of mirtazapine from the tablets before analysis. The concentration of mirtazapine in solutions was determined in the linearity range of 5-25 microg/ml at lambda=315 nm for spectrophotometry and at lambda=220 nm for HPLC and CZE. Spectrofluorimetric determinations were achieved at lambda(excitation)=328 nm and lambda(emission)=415 nm in the linearity range of 2-25 ng/ml. All the methods gave similar results and were validated for selectivity, linearity, precision and sensitivity. Spectrometric methods gave slightly higher RSD values (up to 2.54%). The four methods were directly and easily applied to the pharmaceutical preparation with accuracy, resulting from recovery experiments between 99.72% in HPLC and 101.47% in spectrofluorimetry.

Comparison of high-performance liquid chromatography and capillary zone electrophoresis for the determination of parabens in a cosmetic product.

A high-performance liquid chromatographic method (HPLC) and a capillary zone electrophoresis method (CZE) have been developed for the analysis of methylparaben, ethylparaben, propylparaben and butylparaben in a commercial cosmetic product. A very simple extraction procedure with acidified diethylether was developed. The HPLC method involved a C18 reversed-phase column and a gradient of methanol and water-acetic acid (1%). Electrophoretic separation was performed on a fused-silica capillary with a mixed 15 mM tetraborate buffer (pH 9.2) and methanol (85:15, v/v). The calibration curves were linear from 1 to 40 microg/ml in HPLC and from 5 to 200 microg/ml in CZE. The limit of detection in CZE (0.21 microg/ml) was higher than in HPLC (0.05 microg/ml). Repeatability and intermediate precision were satisfactory for both methods (RSD values < 3.23% in HPLC and < 3.26%, in CZE). Only HPLC allowed the separation of butylparaben isomeric forms when CZE analysis was less time and reagents consuming. These results suggest that HPLC and CZE coupled with a simple extraction process are both suitable for parabens determination in cosmetic products.

Determination of urea, allantoin and lysine pyroglutamate in cosmetic samples by hydrophilic interaction chromatography.

A new HPLC method using a Polyhydroxyethyl A column involving hydrophilic interaction chromatography (HILIC) is described for the simultaneous determination of urea, allantoin and lysine pyroglutamate in a cosmetic cream. Validation of the method was accomplished with respect to linearity, repeatability and limits of detection/quantification. Compound recoveries approach 100% with acceptable RSD values. The method is very simple since no derivatisation is necessary. Furthermore, it allows the rapid and direct chromatographic analysis of urea and hence could provide an alternative to other methods used to determine this compound in biological or cosmetic samples.

The cut-closed-reconnected Roux loop.

BACKGROUND: Motility disturbances in the Roux loop can negatively influence the outcome of reflux gastritis; the uncut Roux loop does not have these disadvantages, but is less suitable for clinical application because of staple dehiscence. The reported "cut-closed-reconnected" Roux loop has the same physiological starting points as the uncut Roux loop, but a difference is an extra closure at the site of the seromuscular level. METHOD: The technique of the cut-closed-reconnected Roux loop is described. RESULTS: After 1 year, the clinical findings in 8 patients were as follows: 1 patient free of symptoms, 4 with gastric pain, 2 patients vomited (1 bilious), and 1 felt fullness. CONCLUSION: Dehiscence of the closure could not be demonstrated by endoscopy, barium contrast roentgenography, and HIDA scan.

Determination of a PAF antagonist pharmacophore using combined Molecular Electrostatic Potential and Molecular Lipophilicity Potential.

PAF is a potent lipid mediator involved in many pathological disorders, such as platelet aggregation, immuno-inflammatory reactions, vascular disorders, septic shock and bronchoconstriction. We chose to study the electronic and lipophilic properties of eleven PAF antagonists, comprising five tetrahydrofuran derivatives, four hetrazepines, the ginkgolide BN-52021 and the pyrrolo-thiazole derivative RP-59227. A Molecular Electrostatic Potential (MEP) contour drawn at -25 kCal/Mol shows three electronegative areas in most compounds. Two areas can be considered as analogous to those described in the so-called "Cache-Oreille" (Earmuff) Model. Molecular Lipophilicity Potential (MLP) analysis allows us to characterise one hydrophilic area, localised at the same place as one of the electronegative areas, and two lipophilic areas, of which the biggest draws a typical "sock" contour. These three areas represent the minimal requirements for a high affinity to the PAF receptor. MEP and MLP results are here combined to propose a pharmacophore for PAF antagonists, including two lipophilic areas, two hydrophilic and electronegative areas and an electronegative zone with no particular hydrophilic behaviour.

Molecular modeling of 5-HT3 receptor antagonists: geometrical, electronic and lipophilic features of the pharmacophore and 3D-QSAR study.

If the geometrical pharmacophore of 5-HT3 receptor antagonists has been proposed by different authors, the electronic and lipophilic features of the ligands had to be precised. A 3-D QSAR study has enlightened the importance of three parameters derived from molecular electrostatic and molecular lipophilicity potentials. A multiple linear regression equation has been established. Its predictive character (non specific binding of 3[H]-ICS 205-930) has been tested with success for three different new ligands.

Determination of the coumarin anticoagulant phenprocoumon and metabolites in human plasma, urine and breast milk by high-performance liquid chromatography after solid-phase extraction.

The coumarin anticoagulant phenprocoumon (PH) and metabolites (6-, 7- and 4'-hydroxyphenprocoumon) were analysed in plasma and urine samples from anticoagulated patients using solid-phase extraction and high-performance liquid chromatography with reversed-phase columns and ultraviolet and fluorescence detection; a simpler handling of samples, higher selectivity, precision, accuracy and analytical recovery were obtained compared to analysis using liquid-liquid extraction. Similarly, a method for the analysis of PH in human breast milk was developed to assess the passage of anticoagulants into breast milk in anticoagulated lactating women.

[Transfer of phenprocoumon in breast milk. Is oral anticoagulation with phenprocoumon a contraindication for breastfeeding?]. / Transfer von Phenprocoumon in die Muttermilch. Ist eine orale Antikoagulation mit Phenprocoumon eine Kontraindikation für das Stillen?

UNLABELLED: As the passage of phenprocoumon into human milk has not been studied yet, mothers on oral anticoagulation with Phenprocoumon are advised to stop breastfeeding in order to avoid the potential hazards of vitamin K deficiency haemorrhage in their babies. We analysed the passage of Phenprocoumon into human milk in a breastfeeding mother of a premature baby (gestational age 32 weeks), who required oral anticoagulation on day 19 post partum. The mother was advised to continue collecting her milk with an electric pump, and to resume breastfeeding, if a significant passage of the drug was excluded. Milk Sampling (fore and hind milk pairs (n = 2), for milk (n = 4), 24 h pooled collections) for the Phenprocoumon analyses with an HPLC method was performed on days 27, 28, and 31 when the Quick's Prothrombin time was stable in the therapeutic range (Phenprocoumon plasma concentrations: 1.8-2.2 micrograms/ml). RESULTS: Phenprocoumon was higher in hind than in foremilk. With constant plasma concentrations the variability between different foremilk samples was 26-76 ng/ml. The Phenprocoumon concentration in the 24 h pooled sample was 33 ng/ml. Estimates of the Phenprocoumon secretion into human breast milk should be from pooled milk samples of a 24 h collection. Phenprocoumon in human milk is only about 1/50 of the corresponding maternal plasma concentrations. The estimated daily Phenprocoumon intake from maternal milk in a baby drinking about 200 ml/kg/day is 6-8 micrograms/kg. This is much less the average maintenance requirement for anticoagulation with Phenprocoumon in children (about 50 micrograms/kg/day).(ABSTRACT TRUNCATED AT 250 WORDS)

[Reconstruction of the tibial plateau fracture with arthroscopic monitoring without arthrotomy]. / Reconstructie van de tibiaplateaufractuur onder artroscopische controle zonder artrotomie.

In the period from October 1986 to November 1988 in the Medisch Spectrum Twente of Enschede, 25 patients were treated for a tibial plateau fracture by means of arthroscopic surgery. The mean hospital stay was 18 days. Active movement of the leg was prescribed from the fifth day. The results were very good in 23 and poor in 2 patients. Complications such as wound infections and skin necrosis were not seen. Additional meniscal lesions could be diagnosed and treated better using this surgical technique. In addition, the limited incisions and consequently the avoidance of extensive arthrotomy allowed faster rehabilitation and a higher probability of healing the chondral tissue.