Fungal Planet description sheets: 868-950.

Novel species of fungi described in this study include those from various countries as follows: Australia, Chaetomella pseudocircinoseta and Coniella pseudodiospyri on Eucalyptus microcorys leaves, Cladophialophora eucalypti, Teratosphaeria dunnii and Vermiculariopsiella dunnii on Eucalyptus dunnii leaves, Cylindrium grande and Hypsotheca eucalyptorum on Eucalyptus grandis leaves, Elsinoe salignae on Eucalyptus saligna leaves, Marasmius lebeliae on litter of regenerating subtropical rainforest, Phialoseptomonium eucalypti (incl. Phialoseptomonium gen. nov.) on Eucalyptus grandis × camaldulensis leaves, Phlogicylindrium pawpawense on Eucalyptus tereticornis leaves, Phyllosticta longicauda as an endophyte from healthy Eustrephus latifolius leaves, Pseudosydowia eucalyptorum on Eucalyptus sp. leaves, Saitozyma wallum on Banksia aemula leaves, Teratosphaeria henryi on Corymbia henryi leaves. Brazil, Aspergillus bezerrae, Backusella azygospora, Mariannaea terricola and Talaromyces pernambucoensis from soil, Calonectria matogrossensis on Eucalyptus urophylla leaves, Calvatia brasiliensis on soil, Carcinomyces nordestinensis on Bromelia antiacantha leaves, Dendryphiella stromaticola on small branches of an unidentified plant, Nigrospora brasiliensis on Nopalea cochenillifera leaves, Penicillium alagoense as a leaf endophyte on a Miconia sp., Podosordaria nigrobrunnea on dung, Spegazzinia bromeliacearum as a leaf endophyte on Tilandsia catimbauensis, Xylobolus brasiliensis on decaying wood. Bulgaria, Kazachstania molopis from the gut of the beetle Molops piceus. Croatia, Mollisia endocrystallina from a fallen decorticated Picea abies tree trunk. Ecuador, Hygrocybe rodomaculata on soil. Hungary, Alfoldia vorosii (incl. Alfoldia gen. nov.) from Juniperus communis roots, Kiskunsagia ubrizsyi (incl. Kiskunsagia gen. nov.) from Fumana procumbens roots. India, Aureobasidium tremulum as laboratory contaminant, Leucosporidium himalayensis and Naganishia indica from windblown dust on glaciers. Italy, Neodevriesia cycadicola on Cycas sp. leaves, Pseudocercospora pseudomyrticola on Myrtus communis leaves, Ramularia pistaciae on Pistacia lentiscus leaves, Neognomoniopsis quercina (incl. Neognomoniopsis gen. nov.) on Quercus ilex leaves. Japan, Diaporthe fructicola on Passiflora edulis × P. edulis f. flavicarpa fruit, Entoloma nipponicum on leaf litter in a mixed Cryptomeria japonica and Acer spp. forest. Macedonia, Astraeus macedonicus on soil. Malaysia, Fusicladium eucalyptigenum on Eucalyptus sp. twigs, Neoacrodontiella eucalypti (incl. Neoacrodontiella gen. nov.) on Eucalyptus urophylla leaves. Mozambique, Meliola gorongosensis on dead Philenoptera violacea leaflets. Nepal, Coniochaeta dendrobiicola from Dendriobium lognicornu roots. New Zealand, Neodevriesia sexualis and Thozetella neonivea on Archontophoenix cunninghamiana leaves. Norway, Calophoma sandfjordenica from a piece of board on a rocky shoreline, Clavaria parvispora on soil, Didymella finnmarkica from a piece of Pinus sylvestris driftwood. Poland, Sugiyamaella trypani from soil. Portugal, Colletotrichum feijoicola from Acca sellowiana. Russia, Crepidotus tobolensis on Populus tremula debris, Entoloma ekaterinae, Entoloma erhardii and Suillus gastroflavus on soil, Nakazawaea ambrosiae from the galleries of Ips typographus under the bark of Picea abies. Slovenia, Pluteus ludwigii on twigs of broadleaved trees. South Africa, Anungitiomyces stellenboschiensis (incl. Anungitiomyces gen. nov.) and Niesslia stellenboschiana on Eucalyptus sp. leaves, Beltraniella pseudoportoricensis on Podocarpus falcatus leaf litter, Corynespora encephalarti on Encephalartos sp. leaves, Cytospora pavettae on Pavetta revoluta leaves, Helminthosporium erythrinicola on Erythrina humeana leaves, Helminthosporium syzygii on a Syzygium sp. bark canker, Libertasomyces aloeticus on Aloe sp. leaves, Penicillium lunae from Musa sp. fruit, Phyllosticta lauridiae on Lauridia tetragona leaves, Pseudotruncatella bolusanthi (incl. Pseudotruncatellaceae fam. nov.) and Dactylella bolusanthi on Bolusanthus speciosus leaves. Spain, Apenidiella foetida on submerged plant debris, Inocybe grammatoides on Quercus ilex subsp. ilex forest humus, Ossicaulis salomii on soil, Phialemonium guarroi from soil. Thailand, Pantospora chromolaenae on Chromolaena odorata leaves. Ukraine, Cadophora helianthi from Helianthus annuus stems. USA, Boletus pseudopinophilus on soil under slash pine, Botryotrichum foricae, Penicillium americanum and Penicillium minnesotense from air. Vietnam, Lycoperdon vietnamense on soil. Morphological and culture characteristics are supported by DNA barcodes.

d-α-tocopherol nanoemulsions: Size properties, rheological behavior, surface tension, osmolarity and cytotoxicity.

The aim of this study was the assessment of the physicochemical stability of d-α-tocopherol formulated in medium chain triglyceride nanoemulsions, stabilized with Tween®80 and Lipoid®S75 as surfactant and co-surfactant, respectively. d-α-tocopherol was selected as active ingredient because of its well-recognized interesting anti-oxidant properties (such as radical scavenger) for food and pharmaceutical industries. A series of nanoemulsions of mean droplet size below 90 nm (polydispersity index < 0.15) have been produced by high-pressure homogenization, and their surface electrical charge (zeta potential), pH, surface tension, osmolarity, and rheological behavior, were characterized as a function of the d-α-tocopherol loading. In vitro studies in Caco-2 cell lines confirmed the safety profile of the developed nanoemulsions with percentage of cell viability above 90% for all formulations.

Genetic variability in isolates of Chromobacterium violaceum from pulmonary secretion, water, and soil.

Chromobacterium violaceum is a free-living Gram-negative bacillus usually found in the water and soil in tropical regions, which causes infections in humans. Chromobacteriosis is characterized by rapid dissemination and high mortality. The aim of this study was to detect the genetic variability among C. violaceum type strain ATCC 12472, and seven isolates from the environment and one from a pulmonary secretion from a chromobacteriosis patient from Ilhéus, Bahia. The molecular characterization of all samples was performed by polymerase chain reaction (PCR) sequencing and 16S rDNA analysis. Primers specific for two ATCC 12472 pathogenicity genes, hilA and yscD, as well as random amplified polymorphic DNA (RAPD), were used for PCR amplification and comparative sequencing of the products. For a more specific approach, the PCR products of 16S rDNA were digested with restriction enzymes. Seven of the samples, including type-strain ATCC 12472, were amplified by the hilA primers; these were subsequently sequenced. Gene yscD was amplified only in type-strain ATCC 12472. MspI and AluI digestion revealed 16S rDNA polymorphisms. This data allowed the generation of a dendogram for each analysis. The isolates of C. violaceum have variability in random genomic regions demonstrated by RAPD. Also, these isolates have variability in pathogenicity genes, as demonstrated by sequencing and restriction enzyme digestion.

Biogeographical patterns and determinants of invasion by forest pathogens in Europe.

A large database of invasive forest pathogens (IFPs) was developed to investigate the patterns and determinants of invasion in Europe. Detailed taxonomic and biological information on the invasive species was combined with country-specific data on land use, climate, and the time since invasion to identify the determinants of invasiveness, and to differentiate the class of environments which share territorial and climate features associated with a susceptibility to invasion. IFPs increased exponentially in the last four decades. Until 1919, IFPs already present moved across Europe. Then, new IFPs were introduced mainly from North America, and recently from Asia. Hybrid pathogens also appeared. Countries with a wider range of environments, higher human impact or international trade hosted more IFPs. Rainfall influenced the diffusion rates. Environmental conditions of the new and original ranges and systematic and ecological attributes affected invasiveness. Further spread of established IFPs is expected in countries that have experienced commercial isolation in the recent past. Densely populated countries with high environmental diversity may be the weakest links in attempts to prevent new arrivals. Tight coordination of actions against new arrivals is needed. Eradication seems impossible, and prevention seems the only reliable measure, although this will be difficult in the face of global mobility.

Genetic diversity of Burkholderia (Proteobacteria) species from the Caatinga and Atlantic rainforest biomes in Bahia, Brazil.

The genus Burkholderia (ß-Proteobacteria) currently comprises more than 60 species, including parasites, symbionts and free-living organisms. Several new species of Burkholderia have recently been described showing a great diversity of phenotypes. We examined the diversity of Burkholderia spp in environmental samples collected from Caatinga and Atlantic rainforest biomes of Bahia, Brazil. Legume nodules were collected from five locations, and 16S rDNA and recA genes of the isolated microorganisms were analyzed. Thirty-three contigs of 16S rRNA genes and four contigs of the recA gene related to the genus Burkholderia were obtained. The genetic dissimilarity of the strains ranged from 0 to 2.5% based on 16S rDNA analysis, indicating two main branches: one distinct branch of the dendrogram for the B. cepacia complex and another branch that rendered three major groups, partially reflecting host plants and locations. A dendrogram designed with sequences of this research and those designed with sequences of Burkholderia-type strains and the first hit BLAST had similar topologies. A dendrogram similar to that constructed by analysis of 16S rDNA was obtained using sequences of the fragment of the recA gene. The 16S rDNA sequences enabled sufficient identification of relevant similarities and groupings amongst isolates and the sequences that we obtained. Only 6 of the 33 isolates analyzed via 16S rDNA sequencing showed high similarity with the B. cepacia complex. Thus, over 3/4 of the isolates have potential for biotechnological applications.

Pharmacokinetic and pharmacodynamic characterization of an oral lysophosphatidic acid type 1 receptor-selective antagonist.

Lysophosphatidic acid (LPA) is a bioactive phospholipid that signals through a family of at least six G protein-coupled receptors designated LPA1₋6. LPA type 1 receptor (LPA1) exhibits widespread tissue distribution and regulates a variety of physiological and pathological cellular functions. Here, we evaluated the in vitro pharmacology, pharmacokinetic, and pharmacodynamic properties of the LPA1-selective antagonist AM095 (sodium, {4'-[3-methyl-4-((R)-1-phenyl-ethoxycarbonylamino)-isoxazol-5-yl]-biphenyl-4-yl}-acetate) and assessed the effects of AM095 in rodent models of lung and kidney fibrosis and dermal wound healing. In vitro, AM095 was a potent LPA1 receptor antagonist because it inhibited GTPγS binding to Chinese hamster ovary (CHO) cell membranes overexpressing recombinant human or mouse LPA1 with IC50 values of 0.98 and 0.73 µM, respectively, and exhibited no LPA1 agonism. In functional assays, AM095 inhibited LPA-driven chemotaxis of CHO cells overexpressing mouse LPA1 (IC50= 778 nM) and human A2058 melanoma cells (IC50 = 233 nM). In vivo, we demonstrated that AM095: 1) had high oral bioavailability and a moderate half-life and was well tolerated at the doses tested in rats and dogs after oral and intravenous dosing, 2) dose-dependently reduced LPA-stimulated histamine release, 3) attenuated bleomycin-induced increases in collagen, protein, and inflammatory cell infiltration in bronchalveolar lavage fluid, and 4) decreased kidney fibrosis in a mouse unilateral ureteral obstruction model. Despite its antifibrotic activity, AM095 had no effect on normal wound healing after incisional and excisional wounding in rats. These data demonstrate that AM095 is an LPA1 receptor antagonist with good oral exposure and antifibrotic activity in rodent models.

In vitro elution characteristics of gentamicin- and teicoplanin-loaded CMW1 and Palacos R bone cement.

PURPOSE: To compare the in vitro elution characteristics of CMW1 and Palacos R bone cement loaded with gentamicin, teicoplanin, or in combination. METHODS: Four bone cement discs were prepared for each cement type. Disc 1 contained no antibiotics; disc 2 contained 0.5 g gentamicin; disc 3 contained 2 g teicoplanin; disc 4 contained 0.5 g gentamicin and 2 g teicoplanin. Elution studies were conducted using a fluorescence polarisation immunoassay technique and performed at intervals of 6 weeks. RESULTS: For CMW1, gentamicin and teicoplanin elution levels in combination discs were higher than those in the single antibiotic discs (p < 0.001 & p < 0.06). For Palacos R, gentamicin elution levels in combination discs were higher than those in the single antibiotic discs (p < 0.001), but teicoplanin elution levels in combination discs were lesser than that from the single antibiotic discs (p < 0.02). In single and combination discs, gentamicin elution levels in Palacos R were higher than those in CMW1 (p < 0.001 & p < 0.001). Palacos R eluted more teicoplanin than CMW1, except in combined disc with gentamicin, when less teicoplanin was eluted. CONCLUSION: Antibiotic elution is higher in Palacos R than CMW1. Antibiotic combination in both cement types has the synergistic effect of increasing antibiotic elution, except for teicoplanin from Palacos R. When high elution of gentamicin is required, Palacos R is preferable. When high elution of teicoplanin is required, Palacos R with only teicoplanin is superior to CMW1.

Evidence of Air Trapping During Ex Vivo Lung Perfusion: A Swine Experimental Lung Imaging and Mechanics Study.

Ex vivo lung perfusion (EVLP) allows the ventilation and perfusion of lungs to evaluate their viability for transplantation. The aim of this study is to compare the mechanical, morphologic and functional properties of lungs during EVLP with values obtained in vivo to guide a safe mechanical ventilation strategy. Lungs from 5 healthy pigs were studied in vivo and during 4 hours of EVLP. Lung compliance, airway resistance, gas exchange, and hemodynamic parameters were collected at positive end-expiratory pressure (PEEP) of 5 cm H2O. Computed tomography was performed at PEEP 0, PEEP 5, and total lung capacity (TLC). Lung pressure-volume (PV) curves were performed from PEEP 0 to TLC. Lung compliance decreased during EVLP (53 ± 5 mL/cm H2O vs 29 ± 7 mL/cm H2O, P < .05), and the PV curve showed a lower inflection point. Gas content (528 ± 118 mL vs 892 ± 402 mL at PEEP 0) and airway resistance (25 ± 5 vs 44 ± 9 cmH2O/L∗s-1, P < .05) were higher during EVLP. Alveolar dead space (5% ± 2% vs 17% ± 6%, P < .05) and intrapulmonary shunt (9% ± 2% vs 28% ± 13%, P < .05) increased ex vivo compared to in vivo, while the partial pressure of oxygen to inspired oxygen fraction ratio (PO2/FiO2) did not differ (468 ± 52 mm Hg vs 536 ± 14 mm Hg). In conclusion, during EVLP lungs show signs of air trapping and bronchoconstriction, resulting in low compliance and increased alveolar dead space. Intrapulmonary shunt is high despite oxygenation levels acceptable for transplantation.

Excimer laser ablation in the treatment of total chronic obstructions in critical limb ischaemia in diabetic patients. Sustained efficacy of plaque recanalisation in mid-term results.

This prospective study aims to evaluate the impact of the excimer laser technology as the first-line endovascular treatment of critical limb ischaemia (CLI) in diabetic patients. The protocol allowed the use of laser ablation of obstructive lesions when conventional endoluminal guidewire crossing of the plaque was unsuccessful. We extrapolate the data of consecutive patients treated, who completed at least 12 months of follow-up, extending the observation to a 26-month time frame. During this period, 67 diabetic patients with CLI were brought to the Cath Lab for 'operative angioplasty' and to be treated with endovascular techniques. Of the 67 cases, laser was used on 35 patients to treat 51 lesions. All patients had type C or D occlusive lesions, according to the TACS II classification, showing a single type D plaque or multiple tandem C/D occlusive plaques ranging from 4 to 23 cm in length. The immediate clinical success, defined as restored direct arterial flow to the foot, was 88.2%. The lesions were successfully crossed by laser in 45 out of 51 attempts. Stents were required in 25% of the patients with 21% lesions. Patency rates were assessed using the Kaplan-Meier survival curves. The patency rates of the successfully treated lesions (freedom from target lesion revascularisation) were 96.6% at 12 months and 82.7% at 24 months. Limb-salvage rate at 12 and 24 months were 100% and 94%, respectively. Our study showed that the excimer laser-assisted angioplasty, when feasible, is effective in granting event-free survival in CLI patients with diabetes, and that endoluminal-driven atherectomy allows long-term success in reducing the need of stents in the lower limb arteries.

Study by inverse gas chromatography of the surface properties of milled graphites.

A graphite was milled during 1, 2, 3 and 4h. The milled samples were then examined using inverse gas chromatography (IGC), at infinite and finite concentration conditions. The present work reports the study of the surface properties by IGC of milled graphite samples as a function of the milling time parameter and of the oxygen content.

What I wish I'd learned at dental school.

Background Much concern appears to exist as to the scope and content of contemporary dental school programmes, with the oft-cited criticism being made that dental graduates are 'no longer as good as they used to be'.Aim The aim of this project was to survey the views of dentists - both new graduates and more established practitioners - on aspects of their own dental school training they felt had been deficient as well as commenting on what aspects of dental school education they would like to see improved/enhanced in current times.Methods An invitation to complete an Internet-based questionnaire was emailed to the Fellows and Members of the Faculty of General Dental Practice (UK). Topics in the questionnaire included the respondent's own dental education history, how well they felt their dental school training had covered certain clinical and non-clinical topics; and their opinions on areas they felt should be included in contemporary dental school programmes.Results Six hundred and forty-nine responses were received from 3,348 emailed invitations (response rate = 19.4%). Sixty-one percent (395) of respondents were qualified for 10 years or more. Among clinical skills and techniques, a majority of respondents reported they felt they had not had sufficient teaching/training in dental school in surgical endodontics (76%), conscious sedation (72%), root surface debridement (71%), fixed orthodontic appliances (68%), porcelain veneers (63%), implants (56%) and posterior composites (53%). If designing a new dental school programme, the most common topics respondents would seek to include/increase were business and practice management (21%), communication skills (including patient management and leadership skills) (10%), and increased clinical time and experience (8%).Conclusions The findings of this project are of interest and relevance to those working with student dentists and young dental practitioners. A greater emphasis is needed on the teaching of certain non-clinical subjects such as business and communication skills, while within clinical subjects there is need to refine and expand teaching in identified areas such as exodontia and endodontics.

Doppler-derived mitral deceleration time: an early strong predictor of left ventricular remodeling after reperfused anterior acute myocardial infarction.

BACKGROUND: The relation between remodeling and left ventricular (LV) diastolic function has not yet been fully investigated. The aim of this study was to determine whether early assessment of Doppler-derived mitral deceleration time (DT), a measure of LV compliance and filling, may predict progressive LV dilation after acute myocardial infarction (AMI). METHODS AND RESULTS: Fifty-one patients (aged 61+/-11 years; 6 women) with anterior AMI successfully treated with direct coronary angioplasty underwent 2-dimensional and Doppler echocardiographic examinations within 24 hours of admission, at days 3, 7, and 30 and 6 months after the index infarction. Mitral flow velocities were obtained from the apical 4-chamber view with pulsed Doppler. End-diastolic volume index (EDVI) and end-systolic volume index (ESVI) were calculated with the Simpson's rule algorithm. Patients were divided according to the DT duration assessed at day 3 in 2 groups: group 1 (n=33) with DT >130 ms and group 2 (n=18) with DT

Medullary-type poorly differentiated adenocarcinoma of the large bowel: a distinct clinicopathologic entity characterized by microsatellite instability and improved survival.

PURPOSE: Recent studies suggest the existence of a distinct class of poorly differentiated large bowel adenocarcinomas, usually termed medullary-type adenocarcinomas (MTAs). The aim of the present study was to accurately define the clinical, histopathologic, biologic, and genetic features of this tumor type. MATERIALS AND METHODS: Among 1,265 surgically resected sporadic colorectal carcinomas, 45 MTAs were identified on the basis of the following criteria: predominantly solid growth pattern (at least 70% of the tumor area) and lack of marked nuclear pleomorphism. The clinicopathologic, biologic, and genetic characteristics of MTAs were compared with those of a series of 457 common glandular colorectal adenocarcinomas. RESULTS: The significantly different clinicopathologic features of MTAs were proximal location, large size, invasion into adjacent organs, expanding pattern of growth, low incidence of distant metastases, more frequent conspicuous peritumoral lymphocytic infiltration, and Crohn's-like lymphoid reaction. Furthermore, young patients with MTAs often demonstrated a family history highly suggestive of a hereditary background. Unlike glandular adenocarcinomas, the large majority of MTAs were DNA diploid by flow cytometric analysis (21 of 25, 84%) and p53 negative by immunohistochemistry (36 of 41, 87.8%). In addition, 18 of the 20 MTAs examined by DNA microsatellite analysis demonstrated widespread microsatellite instability (90% of cases). Patients with MTAs showed a better clinical outcome with respect to patients with common poorly differentiated adenocarcinomas (PDAs) (P <.0001) and well- or moderately differentiated adenocarcinomas (WMDAs) (P =.133). In particular, none of the 33 patients with completely resectable stage II and III MTAs developed tumor recurrence during the observation period. Conversely, 24.7% of patients with stage II and III WMDAs and 48.9% of patients with stage II and III PDAs, who had undergone curative surgical resection, died of recurrent disease (P =.01 and P <.0001, respectively). CONCLUSION: All these data strongly indicate that MTAs represent a distinct pathologic entity, with specific histologic appearance and peculiar clinical and genetic features. These tumors need to be classified separately from other poorly differentiated colorectal carcinomas.

The longest, regular polypeptide 3(10) helix at atomic resolution.

A synthetic, terminally blocked homodecapeptide from the C alpha, alpha-dimethylated glycyl residue alpha-aminoisobutyric acid has been analyzed by single-crystal X-ray diffraction and the structure refined to R = 0.073. The compound crystallizes as a perfect 3(10) helix, stabilized by eight consecutive intramolecular N-H . . . O = C hydrogen bonds. This is the first observation at atomic resolution of a regular polypeptide 3(10) helix as long as three complete turns.

Botulinum toxin injection in the treatment of tennis elbow. A double-blind, randomized, controlled, pilot study.

BACKGROUND: A recent report has suggested that local injection of botulinum toxin type A is an effective method of treatment for chronic tennis elbow. The toxin is thought to provide temporary paralysis of the painful common extensor origin, thereby allowing a healing response to occur. To test this theory, we performed a double-blind, randomized, controlled, pilot trial comparing injections of botulinum toxin type A with those of a placebo (normal saline solution) in the treatment of chronic tennis elbow. METHODS: Forty patients with a history of chronic tennis elbow for which all conservative treatment measures, including steroid injection, had failed were randomized into two groups. Half the patients received 50 units of botulinum toxin type A, and the remainder received normal saline solution. The intramuscular injections were performed 5 cm distal to the maximum point of tenderness at the lateral epicondyle, in line with the middle of the wrist. The two solutions used for the injections were identical in appearance and temperature. The results of a quality-of-life assessment with the Short Form-12 (SF-12), the pain score on a visual analogue scale, and the grip strength measured with a validated Jamar dynamometer were recorded before and three months after the injection. RESULTS: Three months following the injections, there was no significant difference between the two groups with regard to grip strength, pain, or quality of life. CONCLUSIONS: With the numbers studied, we failed to find a significant difference between the two groups; thus, we have no evidence of a benefit from botulinum toxin injection in the treatment of chronic tennis elbow.

[Determination of colonic transit time in healthy subjects in Mexico City. Prospective study]. / Determinación del tiempo de tránsito colónico en personas sanas de la Ciudad de México. Estudio prospectivo.

UNLABELLED: Colonic transit time (CTT) is determined by multiple factors; currently, normal values for the Mexican population are not available. In order to get an estimate one must look at the values reported in the international literature, but cultural, ethnical, nutritional and economic differences may lead to different values. OBJECTIVE: To determine the normal values of colonic transit time in healthy people in Mexico City by the use of radiopaque markers. PATIENTS AND METHODS: Prospective, longitudinal and observational study, which included healthy patients ranging from 18 to 60 years old; excluding pregnant women. The whole group of patients was given before breakfast a gelatin capsule which had 20 radiopaque markers inside -the markers were each 2mm long, and were made by the researcher-. After that, they were taken a simple abdominal X-ray film every 24 hours until they totally eliminated the markers. Their eating and defecation habits were evaluated and also the total amount of liquid they consumed. Inferential statistics were used; data was validated with both parametric and non-parametric tests, considering a significance of p < 0.05. RESULTS: A hundred patients were included in the sample in which 48% were female and 52% male, they were divided in three groups: group A (31%)from 18 to 25 years, group B (37%)from 26 to 40 and group C (32%)from 41 to 60 years; there were no important differences in their water consumption, which was in average of 1.87 lts. in 24 hours; also, there were no considerable differences regarding to their meat, vegetables and fruits' consumption, which was in average of 4.4 times a week; the whole group eliminated the markers according to X-rays which was in 54% after 72 hrs, 45% after 48 hrs and 1% after 24 hrs. We can observe an increase of the CTT related to age: in group C 94% eliminated the markers after 72 hrs and there was no significant difference (statistically) with regards to the other groups. A tendency of an increase of CTT with regards to age was observed: in group A, 80% eliminated the markers after 48 hrs, in group B 49% eliminated them after 48 hrs and 51% after 72 hrs and, in group C, 94% eliminated them after 72 hrs without any statistically significant differences among the study groups. CONCLUSION: The CTT in healthy patients is in a 100% of the cases studied lower or equal to 72 hrs with a tendency to increase in relation to age.

Tramadol hydrochloride: pharmacokinetics, pharmacodynamics, adverse side effects, co-administration of drugs and new drug delivery systems.

Tramadol hydrochloride (TrHC) is a synthetic analgesic drug exhibiting opioid and non-opioid properties, acting mainly on the central nervous system. It has been mostly used to treat pain, although its use to treat anxiety and depression has also been documented. These properties arise from the fact that they inhibit serotonin (5-HT) reuptake augmenting 5-HT concentration on the synaptic cleft. Despite this, TrHC has also been described to have several side effects which are mainly due to its fast metabolization and excretion which in turn requires multiple doses per day. To surpass this limitation, new pharmaceutical formulations are being developed intending the protection, target and sustained delivery as well as a reduction on daily dose aiming a reduction on the side effects. In the present work we have revised the efficacy, safety, biological and adverse effects of TrHC, and the added value of developing a novel drug delivery system for topical administration.

Superiority of three-drug combination chemotherapy versus cisplatin-etoposide in advanced non-small cell lung cancer: a randomized trial by the Italian Oncology Group for Clinical Research.

To evaluate the efficacy of a three-drug regimen vs. a two-drug CDDP based combination in the treatment of NSCLC, we conducted a three-arm randomized parallel trial comparing (a) CDDP (120 mg/m2 day 1) + etoposide (100 mg/m2 days 1-3) every 3 weeks (PE--arm A); (b) CDDP (120 mg/m2 every 4 weeks) + mitomycin (8 mg/m2 days 1, 29, 71) + vindesine (3 mg/m2 days 1, 8, 15, 22 every 2 weeks) (MVP--arm B); and (c) CDDP (120 mg/m2 day 1) + mitomycin (6 mg/m2 day 1) + ifosfamide (3 g/m2 day 2) every 3 weeks (MIC--arm C). From May 1989 to April 1992, 393 consecutive previously untreated patients with NSCLC Stage IIIB and IV entered the trial; 373 were evaluable for survival and 360 for response. The response rate was significantly better for both the three-drug regimens compared with PE (Table 3). Logistic regression model showed a significantly better response in patients with a good P.S. and in Stage IIIB. Main toxicity consisted of myelosuppression: neutropenia Grade III-IV was recorded in 14% (arm A), 15% (arm B) and 21% (arm C). Thrombocytopenia Grade III-IV was worst in arm C: 10% vs. 5% (arm A) and 3% (arm B). Nephrotoxicity Grade III-IV was more common in arm C: 3.5%. Toxic deaths were 11 (3%: three in arm A, five in arm B, three in arm C). From our data, the three-drug containing regimens, MVP and MIC, appear more active than the two-drug combination PE in treatment of advanced NSCLC.

p53 expression in colorectal cancer: relation to tumor type, DNA ploidy pattern and short-term survival.

p53 protein expression was evaluated in a series of 204 primary colorectal adenocarcinomas by immunohistochemistry using frozen tissue sections and monoclonal antibody DO-7. Nuclear staining of more than 5% of neoplastic cells was observed in 124 (60.8%) adenocarcinomas, which were classified as p53 positive. p53 immunoreactivity was found to he unrelated to several clinical and pathologic variables, including age and sex of patient, tumor site, tumor stage, grade of differentiation, pattern of growth, degree of peritumoral lymphocytic infiltration, and venous invasion. A strong association was demonstrated between p53 immunostaining and tumor type. Only 4 of 21 mucinous carcinomas examined (19%) were p53 positive. Conversely, 120 of 183 (65.6%) nonmucinous adenocarcinomas showed positive p53 immunostaining (P <.0001). p53 expression also was related to the flow cytometric DNA ploidy pattern, aneuploid carcinomas with DI >1.20 showing higher frequency of p53 overexpression than DNA diploid, and aneuploid tumors with DI < or = 1.20 (P = .0003). No relationship was found between p53 expression and the Ki-67 proliferation index. With respect to the total study population (mean follow-up 33.4 months; range 19-47 months) the duration of overall survival was independent of p53 expression. In the group of 141 patients with stage I, stage II, and stage III disease who had undergone curative resection, positive p53 immunostaining was associated with poorer overall survival (P = .029). Subgroup analysis showed that the reduced survival conferred by p53 overexpression was confined to patients with stage III tumors (P = .027). However, in multivariate analysis, p53 expression failed to demonstrate independent prognostic significance. Our results indicate that immunohistochemical analysis of p53 expression provides valuable information for the understanding of colorectal cancer biology and clinical behavior.

Depressive symptoms and quality of life in home-care-assisted cancer patients.

To examine the prevalence of depressive symptoms and its relationship with quality-of-life domains in home-care cancer patients at an advanced stage of illness, 86 patients were given psychological tests for depression (Hospital Anxiety Depression Scale) (HAD) and quality of life (EORTC-QLQ-C30) 1 week after admission to the home-care program. Using a proper cut-off score on the HAD-Depression subscale, depressive symptoms were reported by 45% of the patients. The quality of life of depressed patients was more affected than non-depressed patients in the social, emotional, cognitive, and physical domains. Significant correlations were found between depression scores and impairment in most quality-of-life areas. These findings support the importance of depression and quality-of-life evaluation in patients with advanced cancer who are followed in a home-care setting. This evaluation is needed to provide patients, their families, and caregivers with appropriate psychosocial interventions.