Clinical variables and their relation to visual outcome after vitrectomy in eyes with diabetic retinal traction detachment

Background To analyse vitrectomy results in diabetic eyes with retinal traction detachment and to investigate which variables are associated with a worse visual outcome.Methods Forty-four diabetic eyes (33 patients) with central retinal traction detachment were analyzed retrospectively.Results After a median follow-up of 10 months, median visual acuity significantly improved from 20/800 to 20/160 (P=0.02), despite the fact that the majority of patients had a long-standing macular traction detachment (median 120 days). Twenty-two eyes (50%) achieved a visual acuity of >20/200. The retina was finally reattached in 38 eyes (86.3%). Univariate analysis showed that patients with type 2 diabetes, age older than 50 years, preoperative visual acuity <20/200, iris neovascularisation and macular detachment of >30 days had a significantly worse final visual outcome. After multiple logistic regression analysis, age and iris neovascularisation were the strongest predictors of a worse visual outcome; if both were present, the chance of a obtaining a visual outcome of <20/200 was almost 90%.Conclusions Age and iris neovascularisation were the strongest predictors for a low visual outcome. In a review of vitrectomy studies in eyes with severe diabetic traction detachment in the past 2 decades, we found a trend towards higher anatomic success rates, while visual outcome only slightly improved. The current study confirmed the importance of ophthalmic variables, but also indicates the importance of evaluating systemic variables in larger series in order to predict which eyes may truly benefit from vitrectomy.The authors have not received any financial support. The authors have no proprietary interest related to this article.     

Pharmacogenetics of paraoxonases: a brief review

The human paraoxonase (PON) gene family consists of three members, PON1, PON2, and PON3, aligned next to each other on chromosome 7. By far the most-studied member of the family is the serum paraoxonase 1 (PON1), a high-density lipoprotein-associated esterase/lactonase. Early research focused on its capability to hydrolyze toxic organophosphates, and its name derives from one of its most commonly used in vitro substrates, paraoxon. Studies in the last 2 decades have demonstrated PON1's ability to protect against atherosclerosis by hydrolyzing specific derivatives of oxidized cholesterol and/or phospholipids in oxidized low-density lipoprotein and in atherosclerotic lesions. Levels and genetic variability of PON1 influence sensitivity to specific insecticides and nerve agents, as well as the risk of cardiovascular disease. More recently, the other two members of the PON family, PON2 and PON3, have also been shown to have antioxidant properties. A major goal in present research on the paraoxonases is to identify their natural substrates and to elucidate the mechanism(s) of their catalytic activities.     

Use of nutritional supplements to increase the efficacy of fluoxetine in the treatment of anorexia nervosa

OBJECTIVE: Selective serotonin reuptake inhibitor (SSRI) medication does not appear to be effective in ill, malnourished anorexia nervosa (AN) patients. However, it may be effective in preventing relapse after weight restoration. The purpose of this study was to determine whether nutritional supplements could potentiate the effects of fluoxetine in underweight AN subjects. METHOD: Twenty-six subjects with AN participated in a trial of fluoxetine. In a double-blind, placebo-controlled manner, subjects received either nutritional supplements or a nutritional placebo. The nutritional supplement included tryptophan (the precursor of serotonin), vitamins, minerals, and essential fatty acids believed to influence serotonin pathway function. RESULTS: There was no significant difference in weight gain between subjects treated with fluoxetine plus nutritional supplements versus fluoxetine plus a nutritional placebo. Moreover, there were no significant differences between groups on mean changes in anxiety or obsessive and compulsive symptoms. DISCUSSION: The results of this study suggest that supplement strategies are not a substitute for adequate nutrition and are ineffective in increasing the efficacy of fluoxetine in underweight AN subjects.     

Uterine fibroids risk and history of selected medical conditions linked with female hormones

To understand the role of several medical conditions on the risk of uterine fibroids, we analysed the findings of a large case-control study. Cases were 843 women aged 54 or less (median age 43 years, range 21-54) with histologically confirmed uterine fibroids, whose clinical diagnosis dated back no more than 2 years. Indications for surgery were recurrent menorrhagia or ultrasound evidence of fibroids larger than 10 cm in diameter. Controls were 1557 women aged 54 years or less of comparable quinquennia of age (median age 43 years, range 21-54) who had not undergone hysterectomy and were admitted for acute, non-gynecologic, non-hormonal, non-neoplastic conditions to a network of hospitals with a similar catchment area. Clinical history of severe overweight was inversely associated with the risk of fibroids (multivariate odds ratio (OR), OR: 0.6, 95% confidence intervals (CI): 0.5-0.8). An increase in the frequency of fibroids was seen in women with a history of benign breast disease (OR: 1.2, 95% CI: 0.9-1.6) and particularly of breast biopsies (OR: 2.0, 95% CI: 1.2-3.5). The results of this large dataset indicate that medical conditions known or likely to be related to female hormones are not important determinants of the risk of fibroids.     

Recommendations for the assessment of TNT toxicity in sediment

Previous investigations of the ecotoxicity of TNT in spiked sediments noted the rapid degradation and disappearance of the toxicant, yet little is understood regarding the effects of this process on toxicity and subsequent derivation of toxicity reference values. We conducted environmental fate studies and 28-d sediment toxicity tests with benthic oligochaete worms (Tubifex tubifex) with sediments spiked at three different TNT concentrations (440, 1,409, and 4,403 nmol/g dry wt) aged for 1, 8, and 29 d. Because of rapid degradation of TNT, disappearance of degradation products, and partitioning to overlying water, only 25 to 40% of the added nitroaromatic mass balance was associated with sediment immediately after spiking. Lethal toxicity decreased with aging time and was best described by measured sediment nitroaromatic concentrations (sum of TNT and degradation products) at the beginning of exposure, with a median lethal concentration of nitroaromatic compounds of 184 nmol/g dry weight. To accurately describe the ephemeral exposure doses of TNT and its degradation products during toxicity tests with spiked sediments, we suggest that sediments should be aged at least 8 to 14 d after spiking, exposure should be based on measured sediment concentrations or chemical measures of availability, exchange of overlying water should be avoided or minimized, and short-term toxicity tests should be considered.     

Mortality from cutaneous malignant melanoma in Europe. Has the epidemic levelled off?

Trends of mortality from cutaneous malignant melanoma (CMM) between 1960 and 1999 in several European countries and the European Union (EU) as a whole have been reviewed, using death certification data for skin cancer available from the World Health Organization. Separate analyses were performed for young (i.e., age 20-44 years) and middle-aged (i.e., age 45-64 years) adults, among whom around 80-90% of skin cancer deaths are attributable to CMM. After steady rises between 1960 and 1990, skin cancer rates among young adults have tended to decline since the mid-1990s in several European countries, with a fall of 14% in men and of 11% in women in the EU as a whole. In middle-aged adults, the trends were less favourable, although mortality started to level off since the mid-1990s. Thus, our data provide further evidence of an improvement of CMM mortality trends in recent years in several European countries. The particularly favourable trends in young people suggest that a further decline in mortality from CMM in Europe is likely to occur within the next few years.     

Effect of glucose stress conditions in BL6T murine melanoma cells

Elevated expression of stress proteins can be a characteristic of human cancer and may be involved in the development of resistance to some types of chemotherapeutic agent. In this paper, the effect of physiological stress conditions, such as glucose deprivation, was investigated in overexpressing nPKCdelta murine melanoma BL6 (BL6T) cells. Glucose stress conditions decreased the proliferative capacity, increasing the percentage of BL6T cells in the G0/G1 phase of the cell cycle. Furthermore, under such conditions, nPKCdelta, whose subcellular localization is cell cycle dependent, showed a cytoplasmic and perinuclear localization by immunohistochemistry, this being typical for cells in G0/G1 phase. Moreover, these cells expressed GRP-78, a known stress protein. On the other hand, glucose depletion enhanced intracellular melanin as well as tyrosinase activity and expression. In summary, these data demonstrate that stress conditions can modify the biological characteristics of BL6T cells, and therefore can select a quiescent cellular population.     

Adjuvant radiotherapy in stage IV diffuse large cell lymphoma improves outcome

The role of adjuvant radiotherapy to sites of nodal bulky disease in patients with aggressive diffuse large cell lymphoma (DLCL), and stage IV remain undefined. We began a prospective controlled clinical trial to evaluate impact in event free survival (EFS) and overall survival (OS) in a large cohort of patients with a longer follow-up. Between 1989 and 1995; 341 patients with aggressive DLCL and presence of nodal bulky disease (tumor mass > 10 cm) in pathological proven complete response after intensive chemotherapy were randomized to received either radiotherapy (involved fields, 40 Gy) or not. The 5-year EFS and OS in radiated patients were respectively: 82% (95% Confidence interval (CI): 70-89%) and 87% (95% 80-99%), that were statistically significant to control group: 55% (41-64%) (P < 0.001) and 66% (95% CI: 51-73%) (P < 0.01) respectively. Radiotherapy was well tolerated, acute toxicity was mild and until now late toxicity did not appear. The use of adjuvant radiotherapy improve EFS and OS and probably the possibility of cure in patients diffuse large cell lymphoma with worse prognostic factors. Thus, we felt that adjuvant radiotherapy will be considered as part of the initial treatment in this setting of patients.     

Heterogeneity of response to imatinib-mesylate (glivec) in patients with hypereosinophilic syndrome: implications for dosing and pathogenesis

Four cases of hypereosinophilic syndrome (HES) treated with the tyrosine-kinase inhibitor imatinib-mesylate are reported. The drug was effective in three patients, but a prolonged clinical and hematological remission was obtained only in one patient, due to appearance of resistance or poor tolerability in the other cases. The dose of imatinib necessary to achieve a response ranged from 100 to 600 mg/d. One patient with evidence of a clonal T-cell population did not respond at all. We confirm the efficacy of imatinib in HES, but we also underline that type and duration of response may be variable. This could be due to different pathogenetic mechanisms of the disease in single patients.     

Abnormal cytogenetics and significant bone marrow plasmacytosis are predictive of early progression and short survival in patients with low tumor mass asymptomatic multiple myeloma

In order to evaluate the prognostic factors for progression and survival in patients with a low tumor mass asymptomatic multiple myeloma (MM), we studied 59 patients who had a long term follow-up. Cytogenetic abnormalities (using conventional cytogenetics) were observed in 14 out of 45 analyzable patients (31%). An abnormal karyotype and a bone marrow (BM) plasmacytosis > 15% were found to be adverse prognostic factors for progression in univariate and multivariate analysis.