The curative role of radiotherapy in adenocarcinoma of the prostate in patients under 55 years of age: a rare cancer network retrospective study.

To determine whether radiation therapy could be an acceptable alternative to surgery in young patients with adenocarcinoma of the prostate, we analysed the outcome of 39 patients aged under 55 with organ confined tumours who received external radiation therapy in a curative intent. Our results suggest that similar local control in younger and older patients can be expected from either external beam radiotherapy or radical prostatectomy.     

A phase I pharmacologic and pharmacogenetic trial of sequential 24-hour infusion of irinotecan followed by leucovorin and a 48-hour infusion of fluorouracil in adult patients with solid tumors.

PURPOSE: In preclinical studies, sequential exposure to irinotecan (CPT-11) then fluorouracil (5-FU) is superior to concurrent exposure or the reverse sequence; a 24-hour infusion of CPT-11 may be better tolerated than shorter infusions. EXPERIMENTAL DESIGN: CPT-11 was first given at four levels (70-140 mg/m(2)/24 hours), followed by leucovorin 500 mg/m(2)/0.5 hours and 5-FU 2,000 mg/m(2)/48 hours on days 1 and 15 of a 4-week cycle. 5-FU was then increased in three cohorts up to 3,900 mg/m(2)/48 hours. RESULTS: Two patients had dose-limiting toxicity during cycle 1 at 140/3,900 of CPT-11/5-FU (2-week delay for neutrophil recovery; grade 3 nausea despite antiemetics); one of six patients at 140/3,120 had dose-limiting toxicity (grade 3 diarrhea, grade 4 neutropenia). Four of 22 patients with colorectal cancer had partial responses, two of which had prior bolus CPT-11/5-FU. The mean 5-FU plasma concentration was 5.1 micromol/L at 3,900 mg/m(2)/48 hours. The end of infusion CPT-11 plasma concentration averaged 519 nmol/L at 140 mg/m(2)/24 hours. Patients with UDP-glucuronosyltransferase (UGT1A1; TA)6/6 promoter genotype had a lower ratio of free to glucuronide form of SN-38 than in patients with >/=1 (TA)7 allele. Thymidylate synthase genotypes for the 28-base promoter repeat were 2/2 (13%), 2/3 (74%), 3/3 (13%); all four responders had a 2/3 genotype. CONCLUSIONS: Doses (mg/m(2)) of CPT-11 140/24 hours, leucovorin 500/0.5 hours and 5-FU 3,120/48 hours were well tolerated.     

Lupane-triterpenes from the leaves ofBrassaiopsis glomerulata

Three known lupane-triterpenes, 3alpha-hydroxy-lup-20(29)-en-23,28-dioic acid (1), 3a-hydroxylup-20(29)-en-23,28-dioic acid 28-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester (acankoreoside A, 2) and 3alpha,11alpha-dihydroxy-23-oxo-lup-20(29)-en-28-oic acid (3) were isolated from the leaves of Brassaiopsis glomerulata (Blume) Regel, a species of Araliaceae family growing in Vietnam. Their structures were determined on the basis of spectroscopic data.     

Close mapping of the focal non-epidermolytic palmoplantar keratoderma (PPK) locus associated with oesophageal cancer (TOC)

Focal non-epidermolytic palmoplantar keratoderma (PPK or palmoplantar ectodermal dysplasia type III) is associated with oesophageal cancer in three families: two large pedigrees located in Liverpool, UK and in the midwestern American states and one smaller family from Germany. In these families, the PPK is inherited as autosomal dominant and has a late onset, usually manifesting between 7 and 8 years of age. The disease is characterised by thickening of the pressure areas of the soles, but is not restricted to the feet and also presents with oral leukokeratosis and follicular hyperkeratosis. The disease locus [previously termed the "tylosis oesophageal cancer gene' (TOC) locus] has been mapped to 17q23-qter by linkage analysis. This region is located telomeric to the keratin 16 gene, in which mutations have been identified in focal PPK families who show no increased cancer risk. We describe the close mapping of this locus to the interval between AFMb054zf9 and D17S1603 using haplotype analysis of additional Genethon markers in the region and show that although the American family is unlikely to be related to either of the other two, the UK and German pedigrees may share a common descent. This work provides a basis for positional cloning and candidate gene analysis in order to identify a gene that may be involved in familial oesophageal cancer.      

Resistance of CD1d-/- mice to ultraviolet-induced skin cancer is associated with increased apoptosis

Inhibition of p53-induced epidermal apoptosis, generation of p53 mutations, and suppressor T cells are the critical events responsible for the induction and development of UV-induced skin cancers. Recently, we demonstrated that CD1d knockout mice were resistant to UV-induced immunosuppression, prompting us to further address the role of CD1d in regulating UV carcinogenesis. We, therefore, investigated the response of wild-type (WT) and CD1d-/- mice to UV carcinogenesis. We found that although 100% of WT mice developed skin tumors after 45 weeks of UV irradiation, only 60% of CD1d-/- mice developed skin tumors. Surprisingly, keratinocytes and fibroblasts from CD1d-/- mice were more sensitive to UV-induced apoptosis and persisted longer than cells derived from WT mice. In addition, epidermis and dermis taken from chronically UV-irradiated CD1d-/- mice harbored significantly fewer p53 mutations than WT mice. Our findings identify an unexpected and novel function for CD1d as a critical molecule regulating UV carcinogenesis, by inhibiting apoptosis to prevent elimination of potentially malignant keratinocytes and fibroblasts.     

The treatment of real dyeing wastewater by the electro-Fenton process using drinking water treatment sludge as a catalyst

This study aims to evaluate the performance of the electro-Fenton process (EFP) using drinking water treatment sludge (DWTS) for the treatment of dyeing wastewater. Effects of operating parameters including pH, electrode distance, applied voltage, operation temperature and time on the electro-Fenton-oxidation of dyeing wastewater were investigated. The decolorization and COD degradation efficiencies of 97.8% and 89.8%, respectively, were achieved indicating almost complete mineralization of organic pollutants after 90 minutes of reaction at pH 4.0, dosage of DWTS of 2.0 g, applied voltage of 20.0 V, electrode distance of 3.0 cm and ambient temperature. The morphology of the sludge and presence of Fe(OH)₃ after Fenton-oxidation were investigated to understand the mechanisms involved. The degradation of COD in EFP was found to fit well the pseudo-first-order kinetic model. The thermodynamic constants of the Fenton oxidation process were also determined and showed that the Fenton-oxidation process was spontaneous and endothermic. This study provides an efficient and low-cost method for the degradation of non-biodegradable pollutants in dyeing wastewater to solve waste using waste.

This study aims to evaluate the performance of the electro-Fenton process (EFP) using drinking water treatment sludge (DWTS) for the treatment of dyeing wastewater.     

A New Retrieval System for Cement-Retained Implant Superstructures: A Technical Report

This article discusses two methods for improving the retrievability of cement-retained implant superstructures. One method involves incorporating a removal screw in the superstructure and the second method uses a small dimple on the abutment, accessed through a vent in the superstructure.     

Incipient ovarian failure associated with raised levels of follicle stimulating hormone and reduced levels of inhibin A in older sheep

In women there is a gradual rise in the basal level of follicle stimulating hormone (FSH) in the years prior to the menopause (pre- menopause) which is thought to be due to a relative lack of ovarian factors reflecting the number of antral follicles present in the ovaries. Experimental animal models for this phenomenon, particularly in mono-ovulatory species, have been lacking due to most animals' relatively short life span. We have available a group of experimental ewes in which the right ovary was removed and the left ovary was autotransplanted to the neck at least 10 years previously, which have been maintained in good health until an age of 12-13 years. Two experiments were conducted with these animals to determine the endocrine and follicular effects of age: a retrospective experiment in the same Finn-Merino ewes (n = 5) when the animals were 6-7 or 12-13 years of age; and a cohort experiment in old (12-13 years, n = 6) and young (2 years, n = 5) ewes of the same breed. In both retrospective and cohort experiments, the concentrations of FSH were significantly higher (P < 0.05) in older animals during the luteal phase when oestradiol secretion was low. This increase in FSH was associated with a decrease in the concentration of inhibin A (P < 0.05) in older animals in both the follicular and luteal stages of the cycle but the concentrations of oestradiol were similar between ages. Although there were significantly fewer antral follicles (P < 0.05) available for development in older ewes during the early luteal phase of the cycle, the ovulation rate was similar to that observed in younger animals (2.0+/-0 vs 2.0+/-4; P > 0.05) but the interval from luteal regression to the onset of the LH surge was longer (P < 0.05) in older animals. In conclusion, the endocrine changes associated with increasing reproductive age in sheep are therefore similar to those observed in women, suggesting that the sheep could be a useful animal model to study the effect of age on human fertility.      

Molecular diagnosis of cutaneous diseases

OBJECTIVES: To provide an update on the molecular procedures used increasingly in the study and diagnosis of a variety of dermatologic malignancies and inflammatory disorders and to explore the potential use of these techniques in clinical dermatology. Herein, we review assays such as G-banding, fluorescence in situ hybridization, comparative genomic hybridization, and spectral karyotyping in conjunction with the polymerase chain reaction and DNA microarrays. DATA SOURCES: PubMed was searched for published articles on molecular diagnosis and dermatologic diseases. STUDY SELECTION: All English-language studies were selected if they provided useful methodologic information or highlighted the usefulness of molecular techniques. DATA EXTRACTION: Only methodologic and qualitative information was extracted. DATA SYNTHESIS: The information was synthesized into 2 sections: one describing the principles of different molecular diagnostic techniques, and the other highlighting the contributions of molecular diagnostic techniques to the understanding and diagnosis of several dermatologic diseases. CONCLUSIONS: A basic understanding of the principles of molecular diagnostic techniques is crucial for the practicing dermatologist to benefit from the increasing number of molecular diagnostic articles appearing in the literature and potentially to apply these methods in clinical practice.     

An open-label pilot study of levetiracetam for essential tremor

The objective of this study was to determine whether levetiracetam warrants further investigation as a treatment of essential tremor (ET). The authors conducted a 4 -week, open label trial of levetiracetam (Keppra, UCB Pharmaceuticals) in 10 patients diagnosed with ET. Patients were assessed with the complete Tremor Rating Scale (TRS), global impression measures, and adverse events at baseline, after 2 weeks low-dose 500 mg bid and at 4 weeks high-dose 1500 mg bid. All 10 subjects (mean age, 68.6 +/- 7.4 years; seven men, 9 with a positive family history of ET) completed the trial. The TRS observed tremor section modestly improved in 8 subjects (P <0.01). The TRS writing section, water pouring section, and activities of daily living section did not change, and visual analog scores did not change. Subjects rated themselves as "much improved" (n=3), moderately improved (n=1), unchanged (n=1), and mildly worse (n=5). Adverse events included dizziness (n=2), sedation (n=1), and nervousness (n=1). Levetiracetam was well tolerated but failed to improve tremor consistently in this small trial.