Imatinib inhibits proliferation of Ewing tumor cells mediated by the stem cell factor/KIT receptor pathway, and sensitizes cells to vincristine and doxorubicin-induced apoptosis.

PURPOSE AND EXPERIMENTAL DESIGN: The stem cell factor/KIT receptor loop may represent a novel target for molecular-based therapies of Ewing tumor. We analyzed the in vitro impact of KIT blockade by imatinib in Ewing tumor cell lines. RESULTS: KIT expression was detected in 4 of 4 Ewing tumor cell lines and in 49 of 110 patient samples (44.5%) by immunohistochemistry and/or Western blot analysis. KIT expression was stronger in Ewing tumors showing EWS-FLI1 nontype 1 fusions. Despite absence of c-kit mutations, constitutive and ligand-inducible phosphorylation of KIT was found in all tumor cell lines, indicating an active receptor. Treatment with KIT tyrosine kinase inhibitor imatinib (0.5-20 micro M) induced down-regulation of KIT phosphorylation and dose response inhibition of cell proliferation (IC(50), 12-15 micro M). However, imatinib administered alone at doses close to IC(50) for growth inhibition (10 micro M) did not induce a significant increase in apoptosis. We then analyzed if blockade of KIT loop through imatinib (10 micro M) was able to increase the antitumor in vitro effect of doxorubicin (DXR) and vincristine (VCR), drugs usually used in Ewing tumor treatment. Addition of imatinib decreased in 15-20 and 15-36% of the proliferative rate of Ewing tumor cells exposed to DXR and VCR, respectively, and increased in 15 and 30% of the apoptotic rate of Ewing tumor cells exposed to the same drugs. CONCLUSIONS: Inhibition of Ewing tumor cell proliferation by imatinib is mediated through blockade of KIT receptor signaling. Inhibition of KIT increases sensitivity of these cells to DXR and VCR. This study supports a potential role for imatinib in the treatment of Ewing tumor.     

Discrimination between normal and glaucomatous eyes with the Topographic Scanning System: a preliminary report.

BACKGROUND AND OBJECTIVE: To evaluate the ability of the Topographic Scanning System (TopSS; Laser Diagnostic Technologies, San Diego, CA) to differentiate individuals with glaucoma from normal subjects. PATIENTS AND METHODS: The subjects were divided into two groups: primary open-angle glaucoma and normal. All individuals underwent a complete ophthalmic evaluation, a 24-2 full threshold Humphrey visual field evaluation, and a TopSS examination. Cut-off points were selected, receiver operator characteristic (ROC) curves were created, and sensitivity and specificity were calculated for individual TopSS parameters and combinations of variables using multivariate analysis. RESULTS: One hundred twelve patients with glaucoma and 88 normal individuals were enrolled in the study. The best TopSS individual parameters were: average disc diameter (sensitivity: 64%, specificity: 89%, area under ROC curve: 0.824), total disc area (sensitivity: 85%, specificity: 66%, area under ROC curve: 0.802), and cup area (sensitivity: 69%, specificity: 85%, area under ROC curve: 0.797). The multivariate analysis resulted in an area under the ROC curve of 0.91 (sensitivity: 90%, specificity: 81%). CONCLUSIONS: This preliminary report suggests that the use of a multivariate discriminant formula may enhance the ability to differentiate individuals with glaucoma from normal subjects with the TopSS, with high sensitivity and specificity. Further studies investigating a random population are needed to test the validity of this formula.     

Transient evoked otoacoustic emissions pattern as a prognostic indicator for hearing preservation in acoustic neuroma surgery.

OBJECTIVE: To determine whether pre-operative transient otoacoustic emission (TEOAE) patterns are predictive of successful hearing preservation in acoustic neuroma surgery. STUDY DESIGN: Retrospective observational study. SETTING: Tertiary referral medical center. PATIENTS: A convenience sample was identified in whom pre-operative TEOAE data were available in patients undergoing acoustic neuroma surgery from 1993-2004. Ninety-three patients were identified who met this inclusion criterion. INTERVENTIONS: Subjects underwent attempted hearing preservation surgery via middle cranial fossa or retrosigmoid approaches. Routine audiometry, ABR, and TEOAE. MAIN OUTCOME MEASURES: Pre- and post-operative pure tone and speech results were categorized into hearing classes A, B, C, and D as described in the American Academy of Otolaryngology guidelines (1995). Hearing preservation was defined by maintenance of the pre-operative hearing class or downgrade to within one hearing class post-op. Pre-operative TEOAE results were divided into five frequency bands and described as positive in each band if there was a response above the noise floor with >50% reproducibility. RESULTS: Hearing was preserved in 51 patients (55%). Of these, 11 (22%) had positive TEOAE response in all five frequency bands measured (1, 1.5, 2, 3, 4 kHz), whereas 40 (78%) had TEOAE responses ranging from 0 to 4 frequency bands. 42 patients failed to preserve their hearing. Of these, only three (7%) had positive TEOAE in all five frequency bands, and 39 (93%) had TEOAE responses ranging from 0 to 4 frequency bands (p<0.05). Other variables of prognostic significance to hearing preservation in our series included smaller tumor size, tumor location within the IAC, better pre-operative hearing, and shorter latencies on ABR. Logistic regression was then used to compare the prognostic value of TEOAE against these variables. In our series, ABR latencies and 5 frequency band response on TEOAE showed the highest significant correlation to hearing preservation (p<0.05). CONCLUSION: A robust pre-operative TEOAE frequency band pattern may be used as a favorable prognostic indicator for potential hearing preservation in acoustic neuroma surgery. The prognostic value may be enhanced when combined with other prognostic factors such as tumor size, tumor location, pre-operative ABR and audiometric results.     

Análisis de la concentración sérica del ADN tumoral en el cáncer de pulmón no microcítico y avanzado: ¿es útil como factor pronóstico?

INTRODUCTION: Presence of circulating DNA in the serum of patients with cancer makes detection of tumour-specific genetic alterations feasible. OBJECTIVE: To study serum DNA concentration in patients diagnosed as having advanced Non-Small Cell Lung Cancer (NSCLC) and to evaluate its relationship with age, histology, stage, response, time-to-progression (TTP), and survival. METHODS: Serum DNA from 78 patients was purified and spectrophotometrically quantified. RESULTS: No significant correlations were found between serum DNA concentration and age, histology, response and survival. There was a significant correlation with respect to stage (IIIB = 408.75 ng/ml; IV = 478.74 ng/ml; p = 0.02). When patients were grouped according to DNA concentration, significant correlation with TTP was found; establishing a cut-off point at 500 ng/ml ([DNA] < 500 ng/ml TTP = 7.25 months, 95%CI: 3.5-5.25; [DNA ] > or = 500 ng/ml TTP = 4.25 months, 95%CI: 2-6.5; p = 0.05). CONCLUSIONS: Using the present method, DNA concentration quantification appears to be simple, but with certain deficiencies due to inter-sample variability and low specificity. This is because total DNA concentration is measured without distinguishing as to whether it is tumour-related. We suggest that there is a correlation between DNA concentration and prognosis which enables an analysis of the natural history of the disease.     

Evaluation of radiation-induced oral mucositis by optical coherence tomography.

PURPOSE: Optical coherence tomography (OCT) imaging was evaluated to determine if radiation-induced mucosal damage could be noninvasively monitored in real time and correlated with histopathologic findings. EXPERIMENTAL DESIGN: Female C3H mice, ages 7 to 9 weeks, four per group, were immobilized in a custom-made Lucite jig and received 0, 15, 22.5, and 25 Gy in a single fraction to their oral cavity. OCT images were acquired of proximal, middle, and distal aspects of the dorsum of the tongue on days 0, 1, 3, 5, and 7 post-irradiation. Animals were sacrificed on day 7 and samples taken for histologic evaluation. OCT images were visually examined and also quantified by image analysis and compared with histologic findings. RESULTS: Tongues removed 7 days post-irradiation showed no visible damage; however, upon staining with toluidine blue, ulcers at the base of the tongue became visible (100% for 25 Gy, 75% after 22.5 Gy, and 0% after 15 Gy). Visual inspection of OCT images qualitatively compared with histologic findings and quantitative image analysis of the OCT images (effective light penetration depth) revealed significant changes 7 days post-irradiation compared with unirradiated controls for the base of the tongue. CONCLUSIONS: OCT allows for direct noninvasive real-time acquisition of digitally archivable images of oral mucosa and can detect radiation-induced changes in the mucosa before visual manifestation. OCT may be a useful technique to quantify subclinical radiation-induced mucosal injury in experimental chemoradiation clinical trials.     

Radioquimioterapia de la enfermedad limitada del carcinoma pulmonar de célula pequeña. ¿Tratamiento concomitante en protocolos asistenciales?

Purpose We retrospectively reviewed our institution’s database to investigate the outcome and impact of combined radiochemotherapy (RT/CT; concomitant or in sequence) in localised small-cell lung cancer (L-SCLC). Material and methods Between January 1995 to November 1999, 79 patients with L-SCLC received combined RT/CT at our Institution. RT was delivered concurrently or sequentially following the CT. Patients with treatment response received additional prophylactic cranial irradiation (PCI). Results Of the patients treated, 54% had received concurrent CT/RT compared to 46% receiving RT following the CT. PCI was administered to 80% of the patients. Complete response was observed in 66% of patients. With a median follow up of 30 months, median overall survival was 15.9 months; 14.3 months for patients who received RT following CT and 21.6 months for those receiving concurrent CT/RT. The type of schedule of combined radiochemotherapy was an independent prognostic factor for survival free of local recurrence, as was additional PCI for distant metastasis-free survival. Conclusions Our results are similar to those reported previously in the literature. The main point of interest is that our patients were non-selected. We strongly support the use of concurrent CT/RT so as to achieve results comparable to the best in the literature.

     

Hérida Regina Nunes SALGADO,et al:Microbiological assay for the determination of azithromycin in ophthalmic solutionsMicrobiological assay for the determination of azithromycin in ophthalmic solutions

IntroductionAzithromyciniscommercializedbypharmaciesinBrazilinophthalmicsolutionform. Despitetheproveneffectivenessandsafetyinitstreatment, thisdrug,untilthen, doesnotpossessamethodologyofstandar dizedanalysisforophthalmicsolutionsinofficialcom pendiumsan…     

Effect of reminder cards on compliance with antihypertensive medication

Objective Poor compliance to antihypertensive medications has been identified as a primary cause of uncontrolled blood pressure (BP), with consequent increases in hypertension‐related morbidity and mortality. Therefore, any measure known to improve compliance should be encouraged. This study assessed the impact of reminder cards on compliance to antihypertensive therapy. Method A field trial was undertaken in pharmacies located in the districts of Lisbon and Porto. Eligible participants comprised those aged 30–74 years, prescribed an angiotensin‐converting enzyme inhibitor (ACEI) in monotherapy, and taken on a once‐daily regimen. Patients were allocated to control group (CG) or intervention group (IG), the latter being provided with a reminder card, an alarm‐type device due to remind the patient of the time to take his medication. Patients were monitored monthly during 3 months for compliance and blood pressure control. Key findings Seventy‐one patients participated in the study (intervention: 35; control group: 36). Compliance was similar between the groups in the first 2 months of follow‐up (97.1% IG vs 94.9% CG at first follow‐up and 97.5% IG vs 94.2% CG at second follow‐up) and higher in the intervention group at the end of the study (97.3% IG vs 87.3% CG; P = 0.011). There were no mean blood pressure differences between compliant and non‐compliant subjects at the end of the study (P value for differences in systolic BP (P_syst) = 0.580; and P value for differences in diastolic BP (P_dlast) = 0.175). Conclusion This small‐scale study indicates a possible positive impact on patients' compliance resulting from the use of reminder cards. However, this needs confirming in larger scale studies with longer monitoring periods.     

Surgical treatment of secondary hyperparathyroidism

BACKGROUND: Surgical treatment in the patient effected by secondary hyperparathyroidism consists in subtotal parathyroidectomy or total parathyroidectomy plus autotransplantation of parathyroid tissue. METHODS: The results obtained with surgical treatment of 6 patients observed in the years 1995-1996 are analyzed. Two glands were hyperplastic in four patients, 3 in the others. Every patient was submitted to a subtotal parathyroidectomy. RESULTS: Postoperative course was marked by transient hypoparathyroidism in one case. After 18 months of follow-up, no recurrences were observed. CONCLUSIONS: It is pointed out that in case of secondary hyperparathyroidism subtotal parathyroidectomy represents the surgical treatment of choice, according with literature data. Otherwise total parathyroidectomy plus autotransplantation, characterized by a more complex surgical technique, lead to the same results.