Ocular photodynamic therapy for serous macular detachment in the diffuse retinal pigment epitheliopathy variant of idiopathic central serous chorioretinopathy

PURPOSE: To describe the anatomical and functional outcome of verteporfin ocular photodynamic therapy (PDT) in serous retinal detachment caused by the diffuse retinal pigment epitheliopathy form of chronic idiopathic central serous chorioretinopathy. DESIGN: Interventional case report. METHOD: A 48-year-old Caucasian man with unilateral exudative retinal detachment from diffuse retinal pigment epitheliopathy and visual acuity of 20/40 was managed with verteporfin PDT applied sequentially in three separate spots targeting all retinal pigment epithelium leaks identified with intravenous fluorescein angiography (IVFA). Outcome measures included visual acuity, biomicroscopic appearance, and leakage on IVFA.Clinical practice.Subretinal fluid resolved within 2 weeks; visual acuity returned to 20/20 with no recurrence at 6 months of follow-up. There was no leakage on IVFA posttreatment and no obvious toxicity.To our knowledge, this is the first report of PDT causing resolution of macular detachment in diffuse retinal pigment epitheliopathy. Its long-term results with regard to the prognosis of the disease and the recurrence rate remain to be evaluated.     

Determination and clinical verification of dose-response parameters for esophageal stricture from head and neck radiotherapy

The purpose of this work is to determine the parameters and evaluate the predictive strength of the relative seriality model. This is accomplished by associating the calculated complication rates with the clinical follow-up records. The study is based on 82 patients who received radiation treatment for head and neck cancer. For each patient the 3D dose distribution delivered to the esophagus and the clinical treatment outcome were available. Clinical symptoms and radiological findings were used to assess the manifestation of radiation-induced esophageal strictures. These data were introduced into a maximum likelihood fitting to calculate the best estimates of the parameters used by the relative seriality model (D₅₀=68.4 Gy, γ=6.55, s=0.22). The uncertainties of these parameters were also calculated and their individual influence on the dose-response curve was demonstrated. The best estimate of the parameters was applied to 58 patients of the study material and their esophageal stricture induction probabilities were calculated to illustrate the clinical utilization of the calculated parameters. The calculation of the biological effective dose (BED) appeared to be significantly sensitive to the applied fractionation correction for complex treatment plans. The relative seriality model was proved suitable in reproducing the treatment outcome pattern of the patient material studied (probability of finding a worse fit=61.0%, the area under the ROC curve=0.84 and χ² test=0.95). The analysis was carried out for the upper 5 cm of the esophagus (proximal esophagus) where all the strictures are formed. Radiation-induced strictures were found to have a strong volume dependence (low relative seriality). The uncertainties of the parameters appear to have a significant supporting role on the estimated dose-response curve.     

Macroprolactinemia. Is treatment necessary?

A 26-year old symptom-free woman was admitted to our Clinic for evaluation of hyperprolactinemia. The patient, who had normal menstrual cycles, was found accidentally to have a cystic adnexal mass and was placed on oral contraceptives (OC) for 3 months. During the first OC-cycle a bilateral breast nipple discharge was noticed and an elevated serum prolactin (PRL) was detected (2.7 nmol/l). The OC was discontinued and bromocriptine therapy was started. Serum PRL levels were restored and spontaneous menses resumed. The Pituitary magnetic resonance imaging (MRI), the anterior pituitary function, assessed by dynamic tests, and the thyroid hormone levels were normal. Upon bromocriptine discontinuation, PRL levels increased to 13.8 nmol/l. Poly-ethylene-glycol precipitation of the patient's serum, in two consecutive measurements, demonstrated the presence of macroprolactinemia. Since the patient was asymptomatic, a dopamine agonist was not resumed. Macroprolactinemia is characterized by most authors, as a benign condition with no clinical implications. However, a number of investigators challenge this view, suggesting that in some cases mild symptomatology is present possibly requiring therapeutic intervention.     

13q deletion in chronic lymphocytic leukemia: characterization of E4.5, a novel chromosome condensation regulator-like guanine nucleotide exchange factor

We report the characterization of a new gene (E4.5) that maps at chromosome band 13q14.3, a chromosomal area frequently deleted in chronic lymphocytic leukemia (CLL) and in other lymphoid malignancies. E4.5 gene encodes for a 4 kb mRNA expressed in various tissues and has an open reading frame of 531 amino acids. The predicted E4.5 protein shows strong homology with the human regulator of chromosome condensation (RCC1) protein, the principal GTP exchange factor for Ran protein. The E4.5 protein contains a BTB domain in its N-terminus, a protein-protein interaction motif. Therefore, we propose that E4.5 is a new member of the RCC1-related guanine nucleotide exchange factor (GEF) family with potent interaction with other proteins and unknown function. Until now, no tumor suppressor genes have been mapped in the 13q14.3 minimal deleted region (MDR) in patients with CLL. It has been proposed that loss of the 13q14.3 MDR may contribute to lymphoid neoplasia by altering the expression/function of genes located on 13q14.3 outside the MDR. The E4.5 is one of these genes with a potential role in the pathogenesis of CLL.     

Telomerase activity and genetic alterations in primary breast carcinomas

It has been proposed that the structural and numerical chromosome abnormalities recorded in breast cancer could be the result of telomere dysfunction and that telomerase is activated de novo to provide a survival mechanism curtailing further chromosomal aberrations. However, recent in vivo and in vitro data show that the ectopic expression of telomerase promotes tumorigenesis via a telomere length-independent mechanism. In this study, the relation between telomerase expression and the extent of chromosomal aberrations was investigated in 62 primary breast carcinomas. Telomerase activity was measured using a polymerase chain reaction-based telomeric repeat amplification protocol assay and 92% of the tumors were found to express telomerase with a relative activity ranging from 0 to 3839.6. Genetic alterations were determined by G-banding and comparative genomic hybridization analysis and 97% of the tumors exhibited chromosomal aberrations ranging from 0 to 44 (average: 10.98). In the overall series, the relationship between telomerase activity levels and genetic changes could be best described by a quadratic model, whereas in tumors with below-average genetic alteration numbers, a significant positive association was recorded between the two variables (coefficient=0.374, P=.017). The relationship between telomerase activity levels and the extent of genetic alteration may reflect the complex effect of telomerase activation upon tumor progression in breast carcinomas.     

Laparoscopic surgery for fistulas that complicate diverticular disease

Background Diverticular disease is complicated by colovesical and colovaginal fistulas in 4–20% of patients. Laparoscopic surgery is usually reserved for selected cases of uncomplicated disease. The aim of this study was to assess the efficacy and effectiveness of laparoscopic surgery in the treatment of those patients.Methods Eighteen patients, 15 with colovesical fistulas and three with colovaginal fistulas, were operated on laparoscopically. Prospectively collected data, associated with technical feasibility, short-term outcome and effectiveness, were analysed.Results Twelve sigmoidectomies, four extended left colectomies and two segmentectomies were performed. Fistulas were treated with simple dissection or mechanical division, and the bladder wall was repaired in two patients. Mean operating time was 237 min (range 165–330).There was one conversion (5.5%) and no post-operative death. Morbidity was 27.7% and included one major complication. Return of gastrointestinal function occurred 2.9 days post-operatively, and the mean hospital stay was 10 days after surgery. During the 5.1-year follow-up period there was one fistula recurrence (5.5%) and no recurrent diverticulitis.Conclusions Laparoscopic one-stage surgery was technically feasible and safe, with low morbidity. Effectiveness appears favourable when compared with open surgery, but prospective randomized studies are necessary to support such a conclusion.     

Do atypical antipsychotics fail to exert cognitive sparing effects?

The aim of the study was to investigate patterns of the P600 component of event-related potentials (ERPs) elicited during a working memory test in 16 male schizophrenic patients experiencing auditory hallucinations before and after treatment with clozapine and olanzapine, and 13 male normal subjects matched for age and educational level. Before treatment, patients showed significantly reduced P600 amplitudes on the right parietal region compared with controls, and when in remission also showed significantly reduced P600 amplitudes located on the right parietal and temporofrontal areas, compared both to themselves before treatment and to normal controls. The patient's memory performance before and after treatment remained significantly lower than that of healthy controls. These findings may indicate that auditory hallucinations in schizophrenia are associated with impaired synchronization of the processes related to target detection, as reflected by the P600. The present study also casts doubts regarding the cognitive sparing effect of atypical antipsychotics, despite the fact that they mediate symptom improvement.     

Radiation and Concomitant Weekly Administration of Paclitaxel in Patients with Glioblastoma Multiforme. A Phase II Study

The present study was conducted to evaluate the activity and toxicity profile of radiation (RT) and concomitant chemotherapy in patients with glioblastoma multiforme (GBM). Thirty-nine patients were treated postoperatively with RT and concomitant administration of paclitaxel. Cranial irradiation was initiated 2–3 weeks postoperatively and was administered in 2.0 fractions, one fraction per day, for 5 consecutive days per week, to a total of 60Gy. Paclitaxel was delivered at a dose of 100mg/m² over 3-h once weekly for 6 weeks.Thirty-three patients received all 6 cycles of paclitaxel according to the protocol. Totally, 217 cycles were delivered all of them at full dose. The median relative dose intensity of paclitaxel was 1 (range 0.88–1.1). Three (7.5%) patients achieved complete and 9 (23%) partial response, while 12 (30.5%) patients demonstrated stabilization of the disease. Side effects from combined chemoradiotherapy were mainly mild. Grade III toxicity included infection (7.5%) and alopecia (5%). Median time to progression was 6 (range 0.9–27) months and median survival 10.7 (range 0.9–39.5+) months.The present study has clearly shown that 100mg/m² of paclitaxel in 1-h infusion weekly can be safely given concomitantly with RT in patients with GBM with manageable toxicity. However, the efficacy of this combined modality treatment does not appear to be superior to that of RT alone.