A congenital anterior urethrocutaneous fistula in a boy whose mother was exposed to ionizing radiations: case report and literature review.

Anterior congenital urethrocutaneous fistula is a rare anomaly that may present in an isolated fashion or in association with other anomalies of the genital urinary tract or anorectal malformations. A case of congenital anterior urethrocutaneous fistula nonassociated with other congenital anomalies in a 3-year-old male whose mother has been exposed to Chernobyl's nuclear fallout is described. The patient was successfully operated with no recurrence. We report a review of the literature about etiology and surgical strategy including the role of ionizing radiations. The congenital anterior urethrocutaneous fistula represents a rare malformation. The etiopathogenesis is unknown.

Primary retroperitoneal müllerian adenocarcinoma: a case report and literature review.

Primary retroperitoneal müllerian adenocarcinoma (PRMA) is an extremely rare clinical entity. We report the case of a 54-year-old woman who presented with a mass in the right lower retroperitoneum, identified during an ultrasound exam. Computed tomography confirmed a retroperitoneal mass measuring 11 cm. The patient underwent laparotomy and the mass was completely excised. The histopathological exam revealed PRMA.

The metabolism and disposition of a potent inhibitor of hepatitis C virus NS3/4A protease.

Compound A ((1aR,5S,8S,10R,22aR)-5-tert-butyl-N-{(1R,2S)-1-[(cyclopropylsulfonyl)carbamoyl]-2-ethenylcyclopropyl}-14-methoxy-3,6-dioxo-1,1a,3,4,5,6,9,10,18,19,20,21,22,22a-tetradecahydro-8H-7,10-methanocyclopropa[18,19][1,10,3,6]dioxadiazacyclononadecino[12,11-b]quinoline-8-carboxamide) is a prototype of a series of subnanomolar inhibitors of genotypes 1, 2, and 3 hepatitis C virus (HCV) NS3/4A proteases. HCV NS3/4A protease inhibitors have demonstrated high antiviral effects in patients with chronic HCV infection and are likely to form a key component of future HCV therapy. Compound A showed excellent liver exposure in rats, which is essential for compounds intended to treat HCV. The compound was mainly eliminated intact in bile and showed greater than dose proportional systemic exposure in rats. Compound A demonstrated time- and temperature-dependent uptake into rat and human hepatocytes and proved to be a substrate for rat hepatic uptake transporter Oatp1b2 and for human hepatic uptake transporters OATP1B1 and OATP1B3. The liver selectivity observed for this compound is likely to be due to transporter-mediated hepatic uptake together with moderate passive permeability. Metabolism was mainly CYP3A-mediated and generated a reactive epoxide on the vinylcyclopropyl sulfonamide moiety that could be quenched by glutathione. Similar metabolic profiles of Compound A were obtained in liver microsomes of rats and humans. The oral bioavailability at 5 mg/kg was low due to extensive hepatic first-pass effect but clearly the intestinal absorption was enough to deliver a high amount of the compound to the liver. The metabolism and disposition properties of Compound A are particularly attractive to support its evaluation as a drug candidate for the treatment of hepatitis C.

Micelles based on polyvinyl alcohol substituted with oleic acid for targeting of lipophilic drugs.

Polymeric micelles based on polyvinyl alcohol substituted with oleic acid were used as vehicles for progesterone and folic acid. The ability of this amphiphilic polymer to entrap lipophilic drugs and to generate stable micelles in aqueous neutral medium makes it a good candidate for drug delivery. The release of the loaded drugs in acidic environments represents another important property of these systems. Size of micelles, their stability, and their drug-loading capacity were evaluated, as well as the in vitro controlled-release profiles at pH 7.4 and 5.5.

Rapid methods for determination of fluoxetine in pharmaceutical formulations.

Two different analytical methods for the quality control of fluoxetine in commercial formulations have been developed and compared: a spectrofluorimetric method and a capillary zone electrophoretic (CZE) method. The fluorescence emission values were measured at lambda=293 nm when exciting at lambda=230 nm. The CZE method used an uncoated fused-silica capillary and pH 2.5 phosphate buffer as the background electrolyte. The extraction of fluoxetine from the capsules consisted of a simple one-step dissolution with methanol/water, filtration and dilution. Both methods gave satisfactory results in terms of precision; the best results were obtained for the electrophoretic method, with RSD% values always lower than 2.0%. The accuracy was assessed by means of recovery studies, which gave very good results, between 97.5 and 102.6%. Furthermore, both methods also have the advantage of being very rapid.

Clear lens phacoemulsification for correction of high myopia.

PURPOSE: To assess phacoemulsification and posterior chamber intraocular lens (IOL) implantation as an effective, safe, and predictable technique for the correction of high myopia. SETTING: University Eye Clinic of Verona, Verona, Italy. METHODS: A series of 25 eyes with myopia higher than -12.0 diopters (D) had clear lens extraction by phacoemulsification and IOL implantation in the capsular bag. The mean postoperative follow-up was 42.92 months +/- 3.76 (SD). RESULTS: No serious intraoperative complications occurred. Uncorrected visual acuity improved in all cases. The mean postoperative best corrected visual acuity improved by an average of 1 line. One case (4.0%) of postoperative retinal detachment (RD) occurred at 12 months. One case (4.0%) of biometric error (3.0 D) occurred. CONCLUSION: Clear lens extraction by phacoemulsification and IOL implantation in a series of highly myopic eyes was effective and had an acceptable predictability and a low rate of complications. Careful evaluation of the retinal periphery by indirect ophthalmoscopy is recommended to avoid postoperative RD.

Transscleral diode laser photocoagulation in refractory glaucoma.

BACKGROUND AND OBJECTIVE: Patients with glaucoma refractory to medical or surgical treatment are difficult to treat. The aim of this study was to evaluate the effect of contact transscleral diode laser cyclophotocoagulation (DLPC) on these patients' intra-ocular pressure (IOP) and visual acuity. PATIENTS AND METHODS: 37 eyes of 36 patients who suffered from refractory glaucoma and who had undergone DLPC, were followed at the Eye Clinic of Verona University for an average of 14 +/- 4 months. The average age was 54 +/- 26 years. IOP, visual acuity and ocular complications were analysed. RESULTS: A total of 71 treatments were given. More than 1 treatment was given in 22 eyes (59%). The mean pretreatment IOP was 33.1 +/- 3.3 mm Hg. At the last follow-up, the mean IOP was 21 +/- 1.6 mm Hg. Mean total medications were reduced from 4.4 +/- 0.5 to 2.4 +/- 0.3. No serious complications occurred in 71 treatments. Visual acuity remained stable in 25 eyes (67.5%), improved in 6 eyes (16.2%) and decreased in 6 eyes (16.2%). CONCLUSIONS: DLPC is effective in lowering IOP in eyes with refractory glaucoma. It also serves to reduce the number of antiglaucoma medications. This procedure is relatively safe. Nevertheless, multiple DLPC applications may be needed.

Comparison of three analytical methods for quality control of clozapine tablets.

Three different analytical methods for the quality control of clozapine in commercial formulations were developed and compared: a liquid chromatographic (LC) method with UV detection, a capillary zone electrophoretic (CZE) method, and a linear scan voltammetric (LSV) method. The isocratic LC procedure used a C18 reversed-phase column; the CZE method used an uncoated fused-silica capillary and phosphate buffer containing polyvinylpyrrolidone as the background electrolyte; the LSV method analyzed clozapine solutions with acidic phosphate buffer as the supporting electrolyte. The 3 methods gave similar and satisfactory results, in terms of precision and accuracy. Repeatability and intermediate precision were good (RSD% < 2.2) and accuracy, resulting from recovery studies, was between 98 and 102%. The rapidity of analysis was high for all 3 methods, especially for the LSV.

Simultaneous determination of all-trans-retinoic acid, beta-carotene, and vitamin A in galenic preparations by liquid chromatography.

The concentrations of vitamin A, beta-carotene, and all-trans-retinoic acid in oral preparations were determined in a single analysis by a method based on isocratic, reversed-phase liquid chromatography (LC). The LC system consisted of a C18 column, a mobile phase of acetonitrile, dichloromethane, methanol, and water and a UV detector set at 330 nm. The linearity ranges were 25-250 ng/mL for trans-retinoic acid and vitamin A, and 100-1,000 ng/mL for beta-carotene. This LC method for the determination of retinoids is simple, precise, and accurate. No extraction procedure is required before the chromatographic analysis; only a suitable dilution is necessary. The method proved to be reliable, fast, and economical. Furthermore, this method is indicative of stability, because it allows for the determination of degradation products such as 13-cis-retinoic acid.

Quality control of benserazide-levodopa and carbidopa-levodopa tablets by capillary zone electrophoresis.

In modern practice, the treatment of Parkinson's disease and syndrome is carried out using pharmaceutical formulations containing a combination of levodopa and a decarboxylation inhibitor (carbidopa or benserazide). Two pharmaceutical formulations were quantified by capillary zone electrophoresis using two procedures which differed only in the kind of background electrolyte used. One procedure used a 25 mM phosphate buffer, pH 2.5, while the second one used a 25 mM borate buffer, pH 8.5. The electrophoretic analysis was carried out using an uncoated fused- silica capillary, a separation voltage of 20 kV with currents typically less than 60 microA, and spectrophotometric detection at 205 nm. Calibration curves were performed for levodopa (concentration range 1-100 microg/mL), for carbidopa and benserazide (1-50 microg/mL), and the plots of the peak area versus concentration were found to be linear with a correlation coefficient better than 0.9990. Satisfactory results were obtained when commercial tablets were analyzed in terms of accuracy (98-102%), repeatability (0.6-2.0%), and intermediate precision (1.1-2.6%).

Separation of antipsychotic drugs (clozapine, loxapine) and their metabolites by capillary zone electrophoresis.

Two antipsychotic drugs (clozapine and loxapine) and six metabolites, N-demethylclozapine, clozapine N-oxide, N-demethylloxapine (amoxapine), 7-hydroxyloxapine, 8-hydroxyloxapine, 8-hydroxyamoxapine, were separated by capillary zone electrophoresis. Variation of pH and ionic strength of the acidic phosphate buffer (pH below 4) did not enable the separation of loxapine and one of its metabolites. Resolution of the single parent drugs and their metabolites was possible in background electrolytes (phosphate, pH 3.5, 60 mmol/l) containing either 0.2% (w/v) polyvinylpyrrolidone as replaceable pseudo-stationary phase, or 0.75 mmol/l beta-cyclodextrin added as complex-forming agent. Full separation of the mixture with baseline resolution of all analytes was obtained with a background electrolyte with heptakis-6-sulfato-beta-cyclodextrin added as negatively charged complexation agent with improved separation selectivity.

Separation of eleven central nervous system drugs by capillary zone electrophoresis.

Several strategies to improve the separation of 11 central nervous system drugs (antipsychotics and antidepressants) with capillary zone electrophoresis were applied: the variation of the pH of the buffering background electrolyte, its ionic strength, addition of inclusion-complex forming beta-cyclodextrin or polyvinylpyrrolidone (PVP), respectively, as a replaceable, soluble, polymeric pseudo-stationary phase. Best separation was achieved at pH 2.5 and 35 mmol/l ionic strength (phosphate buffer), with 0.5% (w/v) PVP.

Intraocular penetration of topical lidocaine 4%.

PURPOSE: To evaluate the intraocular penetration of lidocaine 4% topically applied before phacoemulsification. SETTINGS: Institute of Ophthalmology, University of Verona, and Department of Medical Pharmacology, University of Padua, Italy. METHODS: Thirty eyes having phacoemulsification for senile cataract were anesthetized by topical application of lidocaine 4%. The drug was applied 3 times in 30 minutes in 15 eyes and 6 times in 60 minutes in 15 eyes. At the beginning of surgery, aqueous humor samples were obtained to measure the lidocaine levels. Blood samples were obtained in 6 patients 30 and 60 minutes after aqueous humor collection. The aqueous humor levels were compared with the amount of pain perceived by patients during surgery. RESULTS: Mean aqueous humor lidocaine concentration was 8.68 micrograms/mL +/- 2.43 (SD) after 3 instillations and 23.21 +/- 8.87 micrograms/mL after 6 instillations. Blood levels of lidocaine were negligible. Patients whose intraocular level was below 12 micrograms/mL perceived more pain during surgery. Only 2 eyes had these low levels after 6 instillations. CONCLUSIONS: Topically applied lidocaine 4% effectively penetrates the eye, providing analgesia for phacoemulsification. We suggest at least 6 instillations in the hour preceding surgery. In this study, pain during surgery was primarily related to poor intraocular levels of the anesthetic agent.

Corneal topography and astigmatism after superior sutured 8 mm scleral tunnel incisions.

OBJECTIVES: To verify corneal topography and astigmatism after cataract surgery with 8 mm scleral tunnel incisions closed with a continuous 10-0 nylon suture. SETTING: Institute of Ophthalmology, University of Verona, Italy. METHOD: Twenty eyes were studied for 12 months after cataract extraction with 8 mm, sutured, scleral tunnel incisions. Corneal topography (EyeSys 2.1) was evaluated for the first 5 months. Astigmatism (absolute and induced) was measured by Javal ophthalmometry preoperatively and 1, 7, 30, 60, 90, 150, and 360 days after surgery. RESULTS: In the week following surgery, corneal shape was minimally affected and uncorrected visual acuity was not compromised. Mean with-the-rule induced cylinder was less than 1.00 diopter (D). After 5 and after 12 months, the mean induced cylinder was still less than 1.50 D but with an against-the-rule shift in almost all eyes. CONCLUSIONS: Sutured 8 mm tunnel incisions showed good results in terms of absolute cylinders but late against-the-rule shift could not be avoided.

Secondary implantation of angle-supported anterior chamber and scleral-fixated posterior chamber intraocular lenses.

PURPOSE: To compare the results of secondary implantation of angle-supported anterior chamber intraocular lenses (IOLs) and scleral-fixated posterior chamber lenses. SETTING: Eye Clinic, University of Verona, Italy. METHODS: This study of 68 eyes of 60 patients comprised two groups. In Group A (n = 35), an angle-supported anterior chamber IOL was implanted and in Group B (n = 33), a scleral-fixated posterior chamber IOL. Follow-up was from 12 to 45 months. RESULTS: In Group A, one eye developed a retinal detachment and another, pseudophakic bullous keratopathy. In Group B, one eye had a major intraoperative choroidal hemorrhage and two developed a retinal detachment postoperatively. All other complications were minor. CONCLUSIONS: Although the rate of sight-threatening complications was about 6% for both groups, scleral-fixated posterior chamber IOLs were associated with more intraoperative and postoperative complications than angle-fixated anterior chamber IOLs, and surgery took longer. Thus, anterior chamber IOL implantation should be considered for older patients with relatively good endothelial cell counts.

Cataract surgery in eyes with early cataracts.

This prospective study assessed visual results and subjective rehabilitation after cataract surgery in eyes with a preoperative acuity of 0.4 (20/40) or better. Fifty eyes (50 patients) were entered in the study. Corrected and uncorrected visual acuity, lens opacity, glare disability, and contrast sensitivity were measured before surgery and four months after surgery. Patient satisfaction was also measured. Best corrected visual acuity was 0.54 +/- 0.12 before surgery and 0.95 +/- 0.15 four months after surgery. Uncorrected visual acuity was 0.24 +/- 0.18 before and 0.58 +/- 0.27 after surgery. Impairment of corrected visual acuity from glare decreased from 0.12 +/- 0.09 before surgery to 0.04 +/- 0.08 four months after surgery. Contrast sensitivity at 6 cycles/degree increased from 2.71 +/- 0.94 units to 4.73 +/- 1.09 units. After surgery, 62% of patients judged their vision to be greatly improved, 32% judged it improved, 6% judged it unchanged. The patient's satisfaction was partially related to the improvement in uncorrected visual acuity. We conclude that cataract surgery can benefit eyes with limited visual impairment if the surgery is uncomplicated and IOL power is calculated correctly.

HPR perimetry and Humphrey perimetry in glaucomatous children.

Fifteen children aged less than 11 years, affected by congenital glaucoma, underwent visual field testing using two different methods: conventional computerized perimetry (24-2 Humphrey program) and High Pass Resolution perimetry (Ring test). The aim of the study was to discover which of the two perimetric techniques was more suitable for younger patient. Results showed that HPR perimetry is more suitable to children. Reasons include the short duration of the test (5 min), and the appearance like a pleasant game to 80% of the subjects tested. In addition it proved to be better than Humphrey test because of the minimal possibilities of memorisation with a reproducibility factor of 68% in our sample and because of the reliable results and satisfactory evaluation in 76% of the eyes examined.

Immunoactivity of pidotimod against episodes of recurrent tonsillitis in childhood.

The therapeutic efficacy of the synthetic immunostimulant pidotimod ((R)-3-[(S)-(5-oxo-2-pyrrolidinyl) carbonyl]-thiazolidine-4-carboxylic acid, PGT/1A, CAS 121808-62-6) was evaluated in a double-blind placebo-controlled study in parallel groups in the management of recurrences in 235 children with recurrent tonsillitis. The ambulant study provided for 15 days of treatment with two oral vials of pidotimod 400 mg or placebo daily, in accordance with a randomisation list, 60 days of treatment with one oral vial of pidotimod 400 mg or placebo daily, and a 90-day follow-up period. The total trial period was 165 days. In addition to evaluating the number of tonsillitis recurrences which occurred during the 75 days of treatment and the 90-day follow-up period, the number of days on which the principal symptoms of the illness were present and on which drugs such as antibiotics or anti-inflammatory agents were used concomitantly, as well as the number of days' absence from school, were analyzed. The findings showed that, taking the treatment phase and the three-month follow-up period together, pidotimod significantly reduces the incidence of inflammatory upper airways episodes. The very low incidence of adverse effects, which was the same as that in the placebo group, confirmed the excellent safety of the product.