Clinical efficacy of distigmine bromide in the treatment of patients with underactive detrusor

Purpose: The aim of this study was to assess the clinical efficacy of distigmine bromide, an anti-cholinesterase agent, deemed to improve detrusor function thereby restoring normal voiding patterns in patients suffering from detrusor underactivity. Materials and methods: A total of 27 patients (11 men and 16 women) with poor detrusor function were included in the study. The diagnosis was established using pressure-flow studies. All patients received distigmine bromide at a dose of 5 mg three times daily for 4 weeks and re-attended for a follow-up urodynamic investigation. The results of baseline pressure-flow studies were compared to those after completion of treatment. Results: Treatment with distigmine bromide resulted in a statistically significant reduction of residual volume and percent residual volume, obviating the need for intermittent self-catheterisation in 11 patients. In addition, maximum flow rate and detrusor pressure at maximum flow increased, although not significantly. The drug was generally well tolerated by the majority of patients. Conclusion: Distigmine bromide shows clinical efficacy in patients with poor detrusor function and may therefore be used alternatively in selected cases.     

Prevalence of overweight and obesity among children and adolescents in Thessaloniki-Greece and Kayseri-Turkey

The aim of this study was to investigate the prevalence of overweight and obesity among children and adolescents in the city of Thessaloniki, Greece and in the Kayseri area of Turkey and compare the results. For this purpose, data concerning the weight and height of 2458 Greek school children aged 6-17 years (1226 6-10 years, 1232 11-17 years) and 3703 Turks (1032 6-10 years, 2671 11-17 years) were collected. BMI was calculated. The prevalence of overweight Greek schoolchildren was 22.2% while that of Turks was 10.6%. The obesity prevalence was 4.1% and 1.6%, respectively (total overweight and obese children 26.3% and 12.2%, respectively). In the analyses, the estimations of the prevalence of overweight and obesity are based on the international BMI percentile curves and cut-off points in subjects aged 2-18 years recently established. A significant gender difference was found, males being more overweight and obese compared to females. Finally, the prevalences for both Greeks and Turks were higher in children when compared to adolescents. In conclusion, Greece (as represented by the Thessaloniki area) has one of the highest prevalences of overweight schoolchildren recorded in Europe while Turkey (as represented by Kayseri area) one of the lowest recorded among developed and developing countries. Differences in lifestyle and socioeconomic status in the two regions are most probably responsible for these results.     

A questionnaire survey concerning the most favourable treatment for Graves' disease in children and adolescents

Graves' disease (GD) is the most common cause of juvenile thyrotoxicosis in children and adolescents (1, 2). Three treatment modalities are now available for the treatment of Graves' thyrotoxicosis in childhood: antithyroid drugs (ATD), surgery and radioactive iodine (RAI). However, none of these treatments has been shown to be ideal or clearly superior to the others. Physicians in different countries have different approaches concerning the optimal treatment of juvenile GD.In a European questionnaire study (3), which was conducted by the European Thyroid Association in 1993 and in which 99 individuals or groups from 22 countries participated, it was found that 22 out of 99 physicians from nine countries would consider RAI treatment as the treatment of choice for children with recurrent thyrotoxicosis after surgery, or with recurrent thyrotoxicosis 2 years after ATD. However, RAI is preferred by only a small percentage of physicians for this group of patients in Europe. Hardly any of the respondents chose RAI for the patients with a toxic adenoma or a multinodular toxic goiter (3). On the other hand, in view of the difficulties with medical therapy in children and adolescents, including poor compliance, a high rate of relapse, drug toxicity and continued thyroid enlargement, some eminent American physicians emphasize the safety, simplicity and economic advantages of (131)I ablation which should be considered more commonly in children (4, 5).We had the opportunity to conduct a similar study during a pediatric thyroidology symposium, which was organized by Professors Buyugkebiz and Laron in Izmir (Smyrna) Turkey from 30 October to 1 November 2003. During the congress a questionnaire with the following four questions was circulated among the 120 participants from eight countries who were mainly paediatric endocrinologists. Most of them were from Turkey and the rest, except for one who came from the USA, were Europeans. Sixty-one out of the 120 physicians responded.     

Pegylated liposomal doxorubicin hydrochloride (PLD) and paclitaxel in recurrent or metastatic head and neck carcinoma: a phase I/II study conducted by the Hellenic Cooperative Oncology Group (HeCOG)

A phase I pharmacokinetics and dose-finding study and a phase II study of the combination of pegylated liposomal doxorubicin HCl (PLD) and paclitaxel were conducted in patients with recurrent or metastatic head and neck cancer (HNC). Sixty patients with recurrent or metastatic disease were enrolled in the study: 11 patients in the phase I study and 49 patients in the phase II study. In the phase I study, the initial dose level of PLD was 35 mg/m as a 1-h infusion with escalating increments of 5 mg/m until the maximum tolerated dose (MTD) was reached. A fixed dose of paclitaxel (175 mg/m) was administered as a 3-h infusion. The combination was administered every 28 days. Pharmacokinetic studies performed on 10 patients indicated that the sequence of drug administration did not cause clinically significant modifications in the pharmacokinetics of either drug. The MTD for PLD was 45 mg/m (dose level 3) and the dose-limiting toxicity was febrile neutropenia, occurring in three of five patients. The phase II dose of PLD was 40 mg/m (dose level 2) and a total of 214 cycles were delivered. Grade 3 or 4 neutropenia was observed in 26% patients and febrile neutropenia occurred in 16% of patients. Grade 3 palmar-plantar erythrodysesthesia (PPE) was recorded in only one patient. The overall response rate was 28% for patients with non-nasopharyngeal tumors [95% confidence interval (CI) 15-45%] and 28.6% for the study population (95% CI 17-43%). The median survival for the study population was 9.7 months; 1-year survival was 38%. We conclude that the recommended dose for the combination of PLD and paclitaxel is 40 and 175 mg/m every 28 days, without granulocyte colony stimulating factor support. The combination of paclitaxel with PLD demonstrated activity in recurrent or metastatic HNC, a favorable toxicity profile and relative ease of administration.     

Inhibition of amiodarone-induced lung fibrosis but not alveolitis by angiotensin system antagonists

Earlier work in this laboratory showed that amiodarone induces apoptosis in alveolar epithelial cells by a mechanism inhibitable by angiotensin system antagonists. A variety of recent studies suggests a critical role for alveolar epithelial cell apoptosis in the pathogenesis of lung fibrosis. On this basis we hypothesized that amiodarone-induced alveolar epithelial cell apoptosis and lung fibrosis in vivo might be inhibitable by the angiotensin converting enzyme inhibitor captopril or the angiotensin receptor antagonist losartan. Amiodarone-induced lung fibrosis was induced in male Wistar rats by oral administration over six months. Replicate groups of rats received captopril or losartan in addition to amiodarone. Apoptosis was detected by increased total lung activity of caspase 3 and in situ end labeling (ISEL) of fragmented DNA. Collagen was localized and quantitated by the picrosirius red technique. Alveolar epithelial cell apoptosis was detected in amiodarone-treated animals as early as three weeks after the start of amiodarone administration; by six months exposure, the incidence of alveolar epithelial cell apoptosis was significantly reduced by coadministration of captopril or losartan. Alveolar wall collagen accumulation also was significantly attenuated by captopril (100%) or losartan (74%), but neither agent blunted the accumulation of alveolar macrophages evoked by amiodarone (5.3-fold at 6 months). Lung neutrophil content was unchanged by amiodarone treatment for three weeks or six months. These results indicate that amiodarone induces alveolar epithelial cell apoptosis in vivo that is inhibitable by angiotensin antagonists. They also support the hypothesis that blockade of angiotensin formation or function attenuates amiodarone-induced lung fibrosis irrespective of the severity of alveolitis.     

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.     

Histologic Comparison of Vibrating Guidewire with Conventional Guidewire Technique in an Experimental Coronary In Vivo Model

Purpose: To compare the damage caused by vibrating guidewire manipulation and conventional guidewire manipulation of soft coronary wires in normal sheep coronary arteries. Methods: Using an intact sheep model the two methods of passing a coronary guidewire down a normal coronary artery under fluoroscopic screening control were studied. The resulting arterial damage caused by the two techniques was studied histologically. The severity of damage was scored from 1 (no damage) to 4 (severe damage) and expressed as: (a) percentage of damaged sections, (b) mean damage score per section and (c) percentage of sections suffering the most severe degree of damage (scores 3 and 4). Results: One hundred and sixty-eight sections were studied. The percentage of damaged sections was lower in the vibrating guidewire group (p = 0.004). The mean damage score and the percentage of sections with a damage score of 3 or 4 were smaller in the vibrating guidewire group than in the conventional guidewire manipulation group (p = 0.001 and p = 0.009, respectively). Conclusions: Both methods of guidewire manipulation cause identifiable vascular damage. The extent and severity of damage appear greater when the guidewire is manipulated manually.     

Tumor classification based on gene expression profiling shows that uveal melanomas with and without monosomy 3 represent two distinct entities

Uveal melanoma is the most common intraocular malignancy. About 50% of patients die of metastases, which almost exclusively originate from primary tumors that have lost one chromosome 3 (monosomy 3). To gain insight into the biological mechanisms that underlie the various metastasizing potential of uveal melanoma, we have determined gene expression levels in 20 primary tumors using oligonucleotide microarrays containing 12500 probe sets. The expression measurements of those 7902 genes that were expressed in more than 10% of tumors were analyzed using two different statistical approaches. We used a modified Wilcoxon rank-sum test to identify genes differentially expressed between tumors with and without monosomy 3. Seven genes showed complete loss of expression in tumors with monosomy 3 but were expressed in tumors with disomy 3. Two of them, CHL1 and fls485, are located within or close to the uveal melanoma susceptibility locus UVM2 at 3p25. However, mutation analysis of both genes in eight tumors with monosomy 3 did not reveal structural or epigenetic alteration. To identify tumor classes, we performed unsupervised hierarchical cluster analysis; this approach separated uveal melanomas into two groups. We found that this classification is strikingly robust because, when tested by "resampling," the same grouping is obtained from 47 of 50 subsamples of genes. In clusterings of the three remaining subsamples, the grouping of only one tumor does not conform with the original classification. Excluding this tumor, cluster analyses of subsamples containing as few as 300 randomly chosen genes consistently result in the same classification, thus indicating that the difference between the two tumor classes is pervasive. Interestingly, all of the tumors in one of the groups have disomy 3, whereas all of the others have monosomy 3. Our findings suggest that there are two distinct entities of uveal melanoma that were previously unrecognized because they are not obviously distinguishable by clinicopathological features.