Macular edema induced by phacoemulsification

Purpose: To characterise the association between lens phacoemulsification and the development of macular edema. Methods: We studied 15 patients who underwent lens phacoemulsification in our clinic between January and April 1998 performed by the same surgeon. Ultrasound power and cumulative time was noted. Follow-up was performed at 1 day, 1 week, 1, 3 and 6 months after operation. On each visit corneal thickness, best corrected visual acuity, biomicroscopy and fluorescein angiography were performed. Patients with systemic diseases and/or retinal diseases were not included. Results: Visual acuity was inversely related to the amount of energy delivered during phacoemulsification. In patients who had received more than 1 Joule of energy, fluorescein angiography revealed a higher incidence of blood retinal barrier breakdown. Corneal thickness was not correlated with the ultrasound energy used. Conclusions: Excessive use of power during phacoemulsification may hamper the postoperative evolution of cataract surgery. This revised version was published online in July 2006 with corrections to the Cover Date.     

Study of the antinociceptive action of the ethanolic extract and the triterpene 24-hydroxytormentic acid isolated from the stem bark of Ocotea suaveolens

We describe here the antinociceptive action of the crude extract (CE), the chemical isolation and characterisation and preliminary pharmacological analysis of 24-hydroxytormentic acid, isolated from the stem bark of Ocotea suaveolens (Lauraceae). The CE given by i.p. or p.o. routes, 30 min and 1 h prior, produced significant inhibition of abdominal constrictions caused by acetic acid and also inhibited both phases of formalin-induced licking in mice. The antinociception caused by the CE, given by i.p. and p.o. routes, lasted up to 4 and 2h, respectively. When assessed in the hot-plate test, the CE was inactive. Its antinociceptive action was not associated with non-specific effects such as muscle relaxation or sedation. The antinociception of CE was not influenced by naloxone, L-arginine or DL-p-chlorophenylalanine methyl ester, when assessed against the formalin assay. The triterpene 24-hydroxytormentic acid, given i.p. 30 min before testing, produced significant, dose-related and equipotent antinociceptive action against both phases of formalin-induced licking in mice. These results demonstrate, for the first time, the occurrence of the triterpene 24-hydroxytormentic acid in the stem bark of Ocotea suaveolens, and show that the CE and 24-hydroxytormentic acid exhibit marked antinociception against the neurogenic and the inflamamtory algesic responses induced by formalin in mice. The mechanism by which this compound and CE produces antinociception still remains unclear, but is unlikely to involve the activation of opioid, nitric oxide or serotonin systems or non-specific peripheral or central depressant actions.     

Toxicokinetics of 1,2-diethylbenzene in male Sprague-Dawley rats-part 1: excretion and metabolism of [(14)C]1,2-diethylbenzene.

The excretion and metabolism of neurotoxic 1,2-diethylbenzene (1, 2-DEB) was studied in male Sprague-Dawley rats after i.v. (1 mg/kg) or oral (1 or 100 mg/kg) administration of 1,2-diethyl[U-(14)C]benzene ([(14)C]1,2-DEB). Whatever the treatment, radioactivity was mainly excreted in urine (65-76% of the dose) and to a lower extent in feces (15-23% of the dose), or via exhaled air (3-5% of the dose). However, experiments with rats fitted with a biliary cannula demonstrated that about 52 to 64% of the administered doses (1 or 100 mg/kg) were initially excreted in bile. Biliary metabolites were extensively reabsorbed from the gut and ultimately excreted in urine after several enterohepatic circulations. Insignificant amounts of unchanged 1,2-DEB were recovered in the different excreta (urine, bile, and feces). As reported previously, presence of 1-(2'-ethylphenyl)ethanol (EPE) was confirmed in urine and demonstrated in bile and feces. The two main [(14)C]1,2-DEB metabolites accounted for 57 to 79% of urinary and biliary radioactivity, respectively. Beta-Glucuronidase hydrolysis and electron impact mass spectra results strongly supported their glucuronide structure. Additionally, these two main metabolites were thought to be the glucuronide conjugates of the two potential enantiomers of EPE. The results indicate that the main initial conversion step of the primary metabolic pathway of 1,2-DEB appears to be the hydroxylation of the alpha-carbon atom of the side chain. The presence of two glucuronide conjugates of EPE in the urine in a ratio different from one suggests that the metabolic conversion of 1, 2-DEB is under stereochemical control.     

Pharmacokinetic Study of Triflusal in Elderly Subjects After Single and Repeated Oral Administration

In this study the single-dose and steady-state pharmacokinetics of unchanged triflusal and its metabolite 2-hydroxy-4-trifluoromethylbenzoic acid (HTB) were studied in 12 elderly subjects treated with a single oral administration of 300 mg triflusal and repeated oral administrations of 300 mg triflusal b.i.d. for 13 days. After a single administration, unchanged triflusal is promptly absorbed (t(max) 0.75 h, C(max) 3.83 &mgr;g/mL) and rapidly depleted from the systemic circulation. Its concentration was measurable only up to 1 to 4 h after administration. The apparent terminal half-life was 0.85 h. HTB proves to be quickly generated from triflusal (t(max) 2.00 h, C(max) 39.88 &mgr;g/mL) and slowly eliminated from the body (t = 54.6 h). With the dose regimen proposed, unchanged triflusal does not accumulate in the body. Conversely, HTB plasma concentration builds up progressively toward steady-state levels of approximately 102 &mgr;g/mL after 4 to 5 d of treatment. No substantial change in peak time, elimination rate constant and half-life evaluated after single-dose treatment was observed on multiple-dose regimen for unchanged triflusal and its metabolite HTB. Therefore, our findings do not indicate a time-dependent pharmacokinetics for triflusal. There were no changes in blood pressure, heart rate or laboratory safety date, i.e., biochemical or hematological profiles.     

Nonsteroidal Anti-Inflammatory Drugs and Prostaglandins: Their Interactions and Effects on the Particulate-Induced Inflammatory Process Implicated in Joint Implant-Loosening and on Monosodium Urate Crystal-Induced Inflammation

The objective of this study was to determine the effects of orally administered misoprostol and diclofenac on inflammation caused by particulates in the rat subcutaneous air-pouch model. Subcutaneous air pouches were formed in male Sprague-Dawley rats. The animals were premedicated by gavage with either saline, diclofenac, misoprostol, or both diclofenac and misoprostol. The air pouches were injected with either polymethyl methacrylate particles or monosodium urate crystals, and the pouch fluids were obtained at 1, 6, 24, 48, and 72 h. Leukocyte influx, tumor necrosis factor, neutral metalloprotease activity, and prostaglandin E(2) levels were measured. It was determined that leukocyte influx was inhibited by diclofenac in the acute inflammation caused by monosodium urate crystals only. In all animals receiving diclofenac, prostaglandin E(2) (PGE(2)) levels were reduced, whereas tumor necrosis factor levels were elevated. The elevation of tumor necrosis factor was prevented by the addition of misoprostol. It is concluded that the oral administration of diclofenac or misoprostol can affect levels of specific mediators involved in particulate-induced inflammation in the subcutaneous air pouch.     

Unaltered insulin sensitivity during calcium channel blockade with amlodipine

Summary The sensitivity of peripheral tissues to insulin is of pathophysiological, therapeutic and possibly also of prognostic relevance. Calcium channel blockers are widely used in the treatment of cardiovascular disorders that are commonly associated with decreased insulin sensitivity (S_I). To evaluate the effects of calcium channel blokkade on S_I, glucose homoeostasis and lipid profiles, studies were made of S_I (determined by the Minimal Model Method of Bergman), basal glucose and insulin levels, serum total triglyceride (Tg) and lipoprotein cholesterol (C) fractions and certain other variables in 38 healthy young men (24 y) during placebo and after 3 weeks of calcium channel blockade with amlodipine 5 mg once daily. Measurements were made after 3 days on a standard diet (2200 kcal · day^–1, 45% carbohydrates, 40% fat and 15% proteins) and after an overnight fast. Compared to placebo, amlodipine decreased supine systolic blood pressure (P<0.01). Heart rate, body weight and 24 h urinary sodium excretion were unaltered, and so were fasting plasma glucose (placebo vs amlodipine: 4.86 vs 4.83 mmol·1^–1, respectively) and insulin levels (7.7 vs 7.9 U·ml^–1), S_I (10.5 vs 9.6·10^–4 × min^–1 pro U·ml^–1), serum total Tg, C and lipoprotein C fractions.The findings demonstrate unchanged insulin sensitivity and secretion, as well as lipoprotein regulation, during maintenance administration of 5 mg amlodipine daily to healthy young men.This work was supported in part by the Swiss National Science Foundation     

Ewing's sarcoma of the bone. Anatomoclinical study of 424 cases]

The clinic-epidemiologic and prognostic features of 424 cases of Ewing sarcoma observed at "Rizzoli" Institute between 1972-1990 are reported. The incidence of the tumor was higher in the second decade of life with slight predominance in the male sex. The primary lesion was especially localized in the extremity and the ratio lower/upper extremity was 5/1. We did not find, in contrast with other Authors, differences in height or in incidence of congenital malformations when compared to controls. The pain was the first common symptom at debut (90%) followed by swelling (50%) and fever (40%). Diagnosis was made 5.5 months after the first symptom and the delay was due to wrong diagnosis at debut in 3/4 of the patients. Laboratory tests showed anemia in about half of the patients and increased value of ESR (60%) and LDH (40%). Seventy-one of the patients were metastatic at presentation, none of these patients were still living after three years. At a median follow-up of 9 years 43% of the patients with localized disease, treated with adjuvant and neo-adjuvant chemotherapy remained continuously disease free, 53% developed metastatic disease and/or local recurrences and 2% had a second malignancy. In 24% of the patients metastases and/or local recurrences appeared three years after the beginning of treatment. Better prognosis was observed in female patients, without fever at diagnosis, with tumor localized at extremities and with normal value of hemoglobin, ERS and LDH. Regarding the type of treatment, better results were obtained by surgery of the primary tumor and by chemotherapy with four drugs (vincristine, cyclophosphamide, adriamycin dactinomycin) in comparison to radiotherapy of the primary tumor and chemotherapy with three drugs (vincristine, cyclophosphamide, adriamycin).