Phase I study of temozolomide combined with oral etoposide in children with malignant glial tumors

The treatment of children with malignant glioma remains challenging. The aim of this multicenter phase I study is to establish the recommended dose (RD) of the combination therapy with temozolomide (TMZ) and oral etoposide (VP-16) in children with relapsed or refractory malignant glioma and brainstem glioma at diagnosis. A phase I trial was conducted to establish the maximum tolerated dose (MTD) of TMZ and oral VP-16. This orally administered combination was investigated by a classical 3 + 3 design. Cohorts of patients were enrolled at 4 different levels: (1) TMZ 120 mg/m² on days 1–5 and VP-16 50 mg/m² on days 1–8; (2) TMZ 150 mg/m² on days 1–5 and VP-16 50 mg/m² on days 1–8; (3) TMZ 150 mg/m² on days 1–5 and VP-16 50 mg/m² on days 1–10; (4) TMZ 150 mg/m² on days 1–5 and VP-16 50 mg/m² on days 1–12. Therapy was administered in 28-day courses. A total of 118 courses were administered to 18 patients with a median age of 11.2 years. At dose level 1, none displayed toxicity. Of the 6 patients at dose level 2, 1 patient had dose limiting toxicity (DLT). None of the 3 patients at dose level 3 had DLT. At dose level 4, grade III/IV thrombocytopenia and neutropenia were observed in 2 out of the 6 patients enrolled. Therefore, the MTD was established at dose level 3. The RD for phase II trial in children with malignant glial is TMZ 150 mg/m² for 5 days and VP-16 50 mg/m² for 10 days every 28 days.     

Review on fluoride-releasing restorative materials--fluoride release and uptake characteristics, antibacterial activity and influence on caries formation.

OBJECTIVES: The purpose of this article was to review the fluoride release and recharge capabilities, and antibacterial properties, of fluoride-releasing dental restoratives, and discuss the current status concerning the prevention or inhibition of caries development and progression. METHODS: Information from original scientific full papers or reviews listed in PubMed (search term: fluoride release AND (restorative OR glass-ionomer OR compomer OR polyacid-modified composite resin OR composite OR amalgam)), published from 1980 to 2004, was included in the review. Papers dealing with endodontic or orthodontic topics were not taken into consideration. Clinical studies concerning secondary caries development were only included when performed in split-mouth design with an observation period of at least three years. RESULTS: Fluoride-containing dental materials show clear differences in the fluoride release and uptake characteristics. Short- and long-term fluoride releases from restoratives are related to their matrices, setting mechanisms and fluoride content and depend on several environmental conditions. Fluoride-releasing materials may act as a fluoride reservoir and may increase the fluoride level in saliva, plaque and dental hard tissues. However, clinical studies exhibited conflicting data as to whether or not these materials significantly prevent or inhibit secondary caries and affect the growth of caries-associated bacteria compared to non-fluoridated restoratives. SIGNIFICANCE: Fluoride release and uptake characteristics depend on the matrices, fillers and fluoride content as well as on the setting mechanisms and environmental conditions of the restoratives. Fluoride-releasing materials, predominantly glass-ionomers and compomers, did show cariostatic properties and may affect bacterial metabolism under simulated cariogenic conditions in vitro. However, it is not proven by prospective clinical studies whether the incidence of secondary caries can be significantly reduced by the fluoride release of restorative materials.     

Influence of different bleaching systems on fracture toughness and hardness of enamel

This study evaluated the influence of different bleaching procedures on the fracture toughness and microhardness of enamel. The labial aspects of 72 bovine incisors were prepared for microhardness determination. At baseline, Knoop hardness (KH) determination was conducted on each specimen. Moreover, the fracture toughness (FT) of enamel was assessed using Vickers hardness indentations with a load of 9.8 N. The length of both indentations and enamel cracks were recorded and used for calculation of FT. The samples were divided among six (A-F) groups (n = 12) and sectioned, resulting in a control and an experimental half. The samples were stored in artificial saliva for 10 days. The experimental halves were removed from the saliva and subjected to bleaching according to manufacturers' instructions (A: Opalescence Xtra, B: Opalescence Quick, C: Rapid White, D: Whitestrips, E: Opalescence 10%, F: Opalescence PF 15%). Bleaching with C-F was conducted daily (C: twice per day for 10 minutes, D: twice per day for 30 minutes, E: 8 hours, F: 4 hours), systems A-B were applied on the first and fifth day (A: twice for 10 minutes, B: 1 hour). Finally, Knoop hardness and FT were assessed and statistically compared to baseline values using Wilcoxon-tests (p < 0.05). KH and FT of the controls remained stable during storage in saliva. All bleaching regimens resulted in a statistically significant percentage loss of KH (mean + standard error of means): A: 17.3 +/- 2.8%, B: 8.6 +/- 3.3%; C: 83.5 +/- 0.61%, D: 29.0 +/- 1.9%, E: 9.0 +/- 2.91%, F: 5.4 +/- 2.2%. The percentage changes (mean + standard error of means) of FT in the experimental specimens were as follows: A: 3.9 +/- 9.5%, B: 0.1 +/- 4.7%; D: -8.2 +/- 7.1%, E: -18.9 +/- 4.7%, F: -12.0 +/- 4.7%. Due to severe surface softening, FT could not be determined for the samples in Group C. Applying Opalescence 10% resulted in a significant reduction in FT compared to baseline. In the remaining groups, changes in FT were not statistically significant.     

Subsurface microhardness of enamel and dentin after different external bleaching procedures

PURPOSE: To evaluate the influence of various bleaching systems on subsurface microhardness of enamel and dentin. METHODS: 60 bovine crowns were distributed among seven groups (A: Opalescence Xtra Boost, B: Opalescence Quick, C: Rapid White, D: Whitestrips, E: Opalescence 10%, F: Opalescence PF 15%). The crowns were sectioned and baseline hardness (Knoop) of enamel and dentin was assessed on the sectioned surface at various distances from the enamel surface. The sectioned surface was covered with wax and the enamel was treated for 10 days with the bleaching agents A-F according to manufacturers' instructions. Bleaching with C-F was conducted each day (C: twice per day for 10 minutes, D: twice per day for 30 minutes, E: 8 hours, F: 4 hours), systems A-B were applied on first and fifth days (A: twice for 10 minutes, B: 1 hour). Finally, hardness was re-assessed. Data were statistically analyzed to compare baseline hardness and final hardness in the respective groups (P< 0.05). RESULTS: Analysis showed that in Group C, hardness was significantly reduced in both enamel and dentin. In the remaining groups, significant reduction of hardness was observed up to the following depths [microm] in enamel; A: 250, B: 700, D: 300, E: 150, F: 150. In these groups no significant hardness changes were recorded in subsurface dentin.     

Pulmonary veno-occlusive disease: the role of CT

Objective

The authors sought to evaluate the diagnostic accuracy of high-resolution computed tomography (HRCT) in the detection of pulmonary veno-occlusive disease (PVOD) in patients with pre-capillary pulmonary arterial hypertension (PAH) of unknown aetiology, and to identify the role of CT in diagnosis and therapy.

Materials and methods

The CT scans of 96 patients were retrospectively reviewed and assessed for specific HRCT findings: ground-glass opacities, septal lines and mediastinal lymph nodal enlargement (short diameter ≥1 cm). According to the HRCT findings, patients were divided into PVOD-suspicious and not PVOD-suspicious. Subsequently, a clinical-instrumental evaluation was performed, and the response to therapy and histopathological reports were evaluated.

Results

Radiological evaluation based on HRCT findings revealed 29 patients as PVOD-suspicious and 67 as not PVOD-suspicious. The final diagnosis was PVOD in 22 patients and idiopathic PAH in 74 patients. The CT scan showed 95.5 % sensitivity, 89 % specificity, 72.5 % positive predictive value, and 98.5 % negative predictive value, with a diagnostic accuracy of 90.5 % in identifying patients with PVOD.

Conclusions

Chest CT can be considered a screening test in the assessment of patients with PAH of unknown aetiology, and the radiologist can help the clinician to identify patients with CT findings that make PVOD highly probable.     

Transdermal buprenorphine in children with cancer-related pain

We present three cases of children (aged 3-5 years) in which cancer-related pain was adequately controlled by Transdermal Buprenorphine. The endpoints for evaluating analgesic efficacy consisted of the assessment of pain using a visual scale and the possibility of reducing other pain treatment. Improvement of pain level was demonstrated by the decrease in pain scores, by reduction of the overall amount of medications, especially opioids, and by improvement of uninterrupted sleep. Only limited data is available on the use of Transdermal Buprenorphine in children. In our experience, Transdermal Buprenorphine allowed good analgesia without significant side effects in these three children with cancer-related pain.     

The relationship between neck pain and cervical alignment in patients with temporomandibular disorders

ABSTRACT

Objective: To elucidate the impact of neck pain on cervical alignment in patients with TMDs.

Method: Patients diagnosed with TMDs between November 2013 and November 2015 were included. All subjects underwent lateral cervical X-ray evaluation and completed the RDC/TMD Axis II Biobehavioral Questionnaire for TMDs. Patients with neck pain also completed the Neck Pain & Disability Scale (NPDS). Cervical lordosis angle was measured according to C2-C7 Cobb’s method.

Results: The mean cervical lordosis angle of the whole group (n = 60) revealed hypolordosis (10.9 ± 12.7°). Cervical lordosis angle did not differ between patients with (n = 28) and without (n = 32) neck pain (12.2 ± 12.8° versus 9.8 ± 12.7°, respectively; p = 0.46). TMD-related variables were not correlated with cervical alignment but were moderately correlated with NPDS score, with the exception of TMD-associated disability.

Conclusion: Patients with TMDs have hypolordotic cervical malalignment (tendency toward kyphosis) regardless of neck pain.     

Evaluation of three different AgNOR counting methods in advanced carcinoma of the prostate

We applied the silver staining of nucleolar organizer regions (AgNOR) technique to the pretreatment biopsies of 50 cases of advanced prostate cancer. Three different counting methods were utilized in the enumeration of AgNORs. All methods yielded statistically significant differences of mean AgNOR counts of groups defined by high and low WHO, and by Gleason grades. However, there was overlap among groups, and further analysis of counts by grouping of patients according to their stage, response to treatment, and prognosis was not conclusive. Replicate counts were performed in 10 cases. While intraobserver reproducibility was high by all methods, only the second counting method yielded nonsignificant interobserver variability. There was a significant intratumoral heterogeneity of AgNOR scores. Lack of technical standardization, low reproducibility, and lack of correlation with prognosis limit the use of AgNOR counts in advanced carcinoma of the prostate. &1995 Wiley-Liss, Inc.     

Large-cell calcifying Sertoli cell tumour of the testis: Associated organ anomalies

A case is reported of unilateral, focal large-cell calcifying Sertoli cell tumour (LCCSCT) of the testis associated with complex endocrine disorders and cardiac myxomas. It is believed that there are two distinct groups of patients with this tumour: those who have complex dysplastic syndromes and bilateral and multifocal tumours; and those without any syndromes but who have unilateral and focal tumours. The presented case differs in that, although the patient has a unilateral focal tumour, unique organ anomalies, such as renal agenesis and inferior vena cava duplication, are also present. These anomalies with LCCSCT have not been reported before.