Impact of real-time, dose-escalated permanent seed implant brachytherapy in intermediate-risk prostate cancer.

PURPOSE: To retrospectively evaluate biochemical control and toxicity in patients who underwent 125I seed brachytherapy (BT) for intermediate-risk prostate cancer (PCa). MATERIALS AND METHODS: Between January 2004-December 2014, 395 patients with intermediate-risk PCa underwent 125I BT. Of these, 117 underwent preoperative planning (PP; 145 Gy) and 278 real-time intraoperative preplanning (IoP; 160 Gy). All patients were followed for ≥ 6 months (> 5 years in 48% of patients and > 7 years in 13%). Median follow-up was 59 months. RESULTS: Biochemical relapse-free survival (BRFS) rates at 5 and 8 years were, respectively, 91.7% and 82.1%. By treatment group, the corresponding BRFS rates were 93.5% and 90% for IoP and 89% and 76.8% for PP. The maximum dose to the urethra remained unchanged (217 Gy) despite the dose escalation (from 145 to 160 Gy), without any significant increase in treatment-related toxicity (p = 0.13). Overall toxicity outcomes in the series were excellent, with only 3 cases (0.76%) of grade 3 genitourinary toxicity. CONCLUSION: The real-time intraoperative planning technique at 160 Gy yields better biochemical controls than the preoperative planning technique at 145 Gy. Dose escalation did not increase urinary toxicity. The excellent results obtained with the IoP BT technique support its use as the first treatment option in this patient population.

TRPA1 Channels Mediate Human Gingival Fibroblast Response to Phenytoin.

Drug-induced gingival enlargement (GE) is a frequent adverse effect observed in patients treated with anticonvulsant, immunosuppressant, and some antihypertensive medications-the antiepileptic phenytoin being the main drug associated with GE due to its high incidence (around 50%). The molecular mechanisms behind drug-induced gingival overgrowth are still unknown. By reverse transcription polymerase chain reaction, we demonstrate that the calcium-permeable ion channels TRPA1, TRPV1, and its capsaicin-insensitive isoform TRPV1b are expressed in human gingival fibroblasts (HGFs), the most abundant cellular type in periodontal tissue. Cultured HGFs responded with intracellular calcium elevations to phenytoin and to the canonical TRPA1 agonist allyl isothiocyanate. Application of phenytoin activated a nonselective cationic current in HGFs with a typical signature for TRPA1 channels. Moreover, this activation was blocked by HC030031, a specific TRPA1 blocker. Similarly, the use of shRNAs against hTRPA1 in HGFs reduced TRPA1 expression and activation by phenytoin. In addition, we show that phenytoin increased intracellular calcium levels in cells transfected with mouse or human TRPA1 channels. Responses to phenytoin were not observed in untransfected cells or cells expressing TRPM8 or TRPV1. The activation of HGFs by phenytoin was markedly reduced in the presence of antioxidant vitamins: ascorbic acid, folic acid, and α-tocopherol. By performing cell proliferation assays, we found that phenytoin did not augment the proliferation rate of HGFs. In contrast, alcian blue and picrosirius red staining of long-term HGFs cultures indicated that phenytoin induces extracellular matrix accumulation of collagen. Collectively, these findings support an important role of TRPA1 channels in phenytoin-induced GE, provide insight into the pathophysiologic mechanism, and offer novel therapeutic opportunities for its treatment.

Improvement of coagulation-flocculation process using anionic polyacrylamide as coagulant aid.

A physicochemical treatment (coagulation-flocculation) was applied to a slaughterhouse wastewater, using anionic polyacrylamide as coagulant aid to improve the settling velocity of the flocs formed with the coagulants used: ferric sulphate, aluminium sulphate and polyaluminium chloride. The optimum speed and stirring time for the flocculation stage were ascertained along with the optimum pH and coagulant and coagulant aid doses. The speed and coagulation time were initially set according to recommendations in the literature concerning the treatment of this type of water. Chemical oxygen demand (COD), biochemical oxygen demand at 5 days (BOD5) and total suspended solids (TSS) were recorded at the beginning and end of each experiment in order to monitor the process. Once the optimal conditions had been established, several parameters were measured in order to assess the coagulation-flocculation process: particle number and size, sludge volume, nutrients (ammonia nitrogen, total Kjeldahl nitrogen, albuminoid nitrogen, orthophosphate, total phosphorus) and the residual concentration of iron and aluminium in clarified water. Anionic polyacrylamide, when added with ferric sulphate or polyaluminium chloride led to a significant increase in the settling speed.

Biophysical absorption models for phenyl-alkyl acids in the absence and in the presence of surfactants. Studies in the rat small intestine.

The present study reviews and checks, by means of experimental work, some theoretical principles of a novel absorption-lipophilicity approach (Pl [symbol: see text] 160-Delfina et al., 1987), used to interpret the effects of synthetic surfactants on drug absorption. For this purpose the correlations between intestinal rat gut absorption constants and lipophilicity indexes are analyzed for a group of compounds belonging to a true homologous series (w-phenyl-alkyl carboxylic acids), in the absence and in the presence of polysorbate 80 in the luminal fluid. Evidence is given for the following surfactant actions: (a) at critical micelle concentration (CMC), the surfactant increases membrane polarity and simultaneously nullifies the limiting character of the stagnant aqueous layer adjacent to the membrane; (b) at supramicellar concentrations (SMC) the above actions become almost completely masked by the micellar solubilization of the compounds, which decreases their absorption rate constants. As a consequence of these interactions, correlation between membrane absorption and lipophilicity, which was clearly hyperbolic in free solution, becomes potential in the presence of surfactant at CMC, whereas at SMC a bilinear correlation is found. Pore absorption was much less affected. Mathematical and physiochemical reasons for this behaviour are outlined, and practical implications are briefly discussed.

Striatum gray matter reduction in males with an overactive behavioral activation system.

Using optimized voxel-based morphometry, we studied the relationship between gray matter volume in brain areas associated with reward and scores on a behavioral activation system measure (the Sensitivity to Reward scale) in a sample of 50 male undergraduates. Voxel-based morphometry analysis revealed a negative correlation between Sensitivity to Reward scores and gray matter volume in the dorsal striatum and prefrontal cortex. Results indicate that a reduced volume in the striatum might be associated with enhanced reward sensitivity and deficits in inhibitory control.

Behavioral Inhibition System activity is associated with increased amygdala and hippocampal gray matter volume: A voxel-based morphometry study.

Recent research has examined anxiety and hyperactivity in the amygdala and the anterior hippocampus while processing aversive stimuli. In order to determine whether these functional differences have a structural basis, optimized voxel-based morphometry was used to study the relationship between gray matter concentration in the brain and scores on a Behavioral Inhibition System measure (the Sensitivity to Punishment scale) in a sample of 63 male undergraduates. Results showed a positive correlation between Sensitivity to Punishment scores and gray matter volume in the amygdala and the hippocampal formation, that is, in areas that Gray, J.A., and McNaughton, N.J. (2000). The neuropsychology of anxiety. Oxford: Oxford Medical Publications. associated with the Behavioral Inhibition System.

Roles for redox regulation in leaf senescence of pea plants grown on different sources of nitrogen nutrition.

Leaf senescence and associated changes in redox components were monitored in commercial pea (Pisum sativum L. cv. Phoenix) plants grown under different nitrogen regimes for 12 weeks until both nodules and leaves had fully senesced. One group of plants was inoculated with Rhizobium leguminosarum and grown with nutrient solution without nitrogen. A second group was not inoculated and these were grown on complete nutrient solution containing nitrogen. Leaf senescence was evident at 11 weeks in both sets of plants as determined by decreases in leaf chlorophyll and protein. However, a marked decrease in photosynthesis was observed in nodulated plants at 9 weeks. Losses in the leaf ascorbate pool preceded leaf senescence, but leaf glutathione decreased only during the senescence phase. Large decreases in dehydroascorbate reductase and catalase activities were observed after 9 weeks, but the activities of other antioxidant enzymes remained high even at 11 weeks. The extent of lipid peroxidation, the number of protein carbonyl groups and the level of H(2)O(2) in the leaves of both nitrate-fed and nodulated plants were highest at the later stages of senescence. At 12 weeks, the leaves of nodulated plants had more protein carbonyl groups and greater lipid peroxidation than the nitrate-fed controls. These results demonstrate that the leaves of nodulated plants undergo an earlier inhibition of photosynthesis and suffer enhanced oxidation during the senescence phase than those from nitrate-fed plants.

[Psoas muscle abscess. Description of a series of 19 cases]. / Absceso del músculo psoas. Descripción de una serie de 19 casos.

Abscess of the psoas muscle (PA) is every more frequently observed in recent years. The PA diagnosed in the authors' center over a period of 91 months are presented, analyzing the main clinical features, microbiologic causal agents, risk factors, treatment and the differences between primary and secondary PA. A total of 19 cases of which 14 were secondary PA (73.7%) and 5 primary PA (26.3%) were diagnosed. The main foci of infection of the former were the bone and the genitourinary tract, with intestinal infection being rare. The most frequent clinical data were lumbar pain with possible irradiation to the lower limb, fever, and leucocytosis with neutrophilia. Gram negative and enteric anaerobes were the bacteria most often identified, followed by Staphylococcus aureus and Mycobacterium tuberculosis. In a high percentage of patients (57.8%) a history of immunodeficiency was reported. In regard to treatment, surgical drainage was performed in 5 cases (26.3%), while ten cases (52.6%) were treated by DPCT. Four patients (21%) were exclusively treated with antibiotics. Recurrence was observed in three cases (15.3%) of the DPCT group requiring new drainage. Of all the cases, 18 were cured while one death occurred, being attributed to the underlying tumoral disease of advanced stage. The authors believe DPCT to be a good therapeutic option in both primary and secondary PA, thereby avoiding the risks of major surgery. In the cases with no underlying immunodeficiency the existence of secondary PA should be discarded as occurred in 7 out of 8 cases with no history of immunodeficiency in this series of patients.

Small-cell lung cancer in the elderly--is age of patient a relevant factor?

Different management procedures for diagnosis and treatment of small-cell lung cancer (SCLC) and other tumours in the elderly have been reported, but there is a lack of data from a communal hospital perspective. Information on clinical parameters such as weight loss, co-morbidity, performance status and investigative procedures for staging of disease and inclusion in clinical trials was recorded for patients in the province of Albacete (Spain). Patients' ages were categorized in two groups: under 70 years and 70 years or more, and a comparison of treatment variables, toxicities, response and time to event measures was carried out. Ninety-five patients were referred to our Unit for treatment. Of these patients, 62% were under 70 years of age and 38% were in the older age category. Clinical variables and staging procedures did not differ between groups. Trial assignment showed a bias in favour of younger patients (11 vs. 1, p = 0.02). No differences in the number of patients without treatment were found, but the older group presented fewer cases of optimal (> or = 4 cycles) therapy, less chemotherapy delivery (smaller mean total doses of cisplatin and etoposide) and smaller mean total dose of radiotherapy (57/45 Gy). The response to treatment (46%/50%) toxicity registered and overall survival did not differ between age categories. Age does not seem to be a relevant prognostic factor in this disease. Carefully calculated dose reductions for chemotherapy in elderly patients based on initial performance status and/or toxicity during treatment may be a useful policy without detrimental implications on outcome.

Experimental studies on the influence of surfactants on intestinal absorption of drugs. Cefadroxil as model drug and sodium lauryl sulfate as model surfactant: studies in rat colon.

The effect of the anionic surfactant, sodium lauryl sulfate (CAS 151-21-3), on the absorption of cefadroxil (CAS 50370-12-2) as model antibiotic in colon has been studied by means of an in situ rat gut technique, as a previous step to investigate the influence of the surfactant on the intestinal, carrier-mediated absorption of the antibiotic. Microbial degradation tests were initially performed, which demonstrated that cefadroxil disappearance from luminal content was only due to absorption. Micelle solubilization of cefadroxil was also previously assessed through dialysis tests in order to adequately correct absorption rate constant values found in the presence of the surfactant at supramicellar concentration. Micelle solubilization was minimal, although statistically significant. Apparent passive absorption rate constants, ka(h-1), were determined in the presence of variable concentrations of lauryl sulfate in perfusion fluids. Results showed that ka values greatly increased as surfactant luminal concentration increased until an asymptotic value (about 7-fold higher than cefadroxil alone) was obtained; this was assumed to be due to a direct effect of the surfactant on membrane polarity. Moreover, the results were satisfactorily adjusted using a functional hyperbolic-type equation, as occurs with many other saturable processes. This was supposed to be indicative that the surfactant effect is due to an adsorption process of the surfactant ions or molecules to the intestinal absorbent membrane.

Técnica de compensación mediante uso de segmentos en el tratamiento craneoespinal / Compensation technique using segments in the craniospinal treatment

Propósito: Describir la técnica utilizada en la radioterapia del eje craneoespinal en el Servicio de Oncología Radioterápica del Hospital LA FE, en cuyos campos se utilizan segmentos adicionales para optimizar la distribución de dosis resultante. Material y método: Para todos los pacientes se lleva a cabo una simulación virtual que permite localizar las estructuras críticas y determinar con precisión las colindancias entre los campos. En la planificación dosimétrica tridimensional (3D) se homogeneiza la distribución de dosis en el plano sagital, añadiendo eventualmente segmentos (1 ó 2) que apantallen las zonas sobredosificadas, durante una determinada proporción de las unidades de monitor. Resultados y discusión: La técnica descrita permite una adecuada optimización en este complejo tipo de tratamientos sin variar apenas el tiempo de planificación basada en la simulación virtual (AU)