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Biomedical subjects

M Vincent

Publications and source records attributed to M Vincent.

At least 19 recordsLinked to original sources

Stability of Delta(9)-tetrahydrocannabinol (THC) in oral fluid using the Quantisal collection device.

This article details the stability of Delta(9)-tetrahydrocannabinol (THC) in oral fluid during collection, extraction and storage. Oral fluid is being increasingly used as the specimen of choice for the detection of drug use in various applications. Studies to determine the extraction efficiency of THC from the collection buffer and stability under various laboratory storage conditions were carried out. THC was extracted from the collection pad and buffer with an average efficiency over 80% and was stable in Quantisal oral fluid extraction buffer when stored at refrigerated temperatures. Fluorescent lighting caused THC losses of over 50%, however the presence of the pad reduced the loss. In the dark, the loss of THC at room temperature was approximately 20% over 14 days. When stored with the serum separators in place, THC losses were significant. After 3 days, THC concentration was reduced by almost 30%, and after 14 days, 60% of the drug was lost and the losses were not concentration dependent.

Buffers↗

A National Cancer Institute of Canada Clinical Trials Group Study--IND.135: Phase I/II study of irinotecan (camptosar), oxaliplatin and raltitrexed (tomudex) (COT) in patients with advanced colorectal cancer.

Thirty-one patients with metastatic colorectal cancer were enrolled in this phase I/II trial of a triple combination of camptosar (C), oxaliplatin (O) and tomudex (T), all given on day one of a convenient three-week schedule. Patients received 257 cycles (1-18) in five cohorts. Toxicity was manageable and haematological toxicity was mild to moderate. Diarrhoea was the main dose-limiting toxicity; nausea and vomiting were common. Fatigue was frequent, moderate in severity and a reason for discontinuation in some patients. The recommended phase II doses were (C) 220 mg/m(2), (O) 100mg/m(2), (T) 2.75 mg/m(2). A 50% response rate in 30 evaluable patients was confirmed by an independent radiology review board; progression-free survival and overall median survival were 7.3 months and 16.6 months, respectively. Of the 16 patients treated at the recommended dose, 9 (56.3%) experienced partial response. Further evaluation in a randomized study compared to sequential doublets is warranted. Triple combinations could be relevant in curative settings for high-risk patients.

Adult↗

Initial results for urban metal distributions in house dusts of Syracuse, New York, USA.

A program of house dust sample collection and analysis has begun in Syracuse, New York, USA, in order to determine the feasibility of a geography-based exposure assessment for urban metals. The sampling program, and the protocols it employs, is described for two different types of wipe media, Ghost Wipes and Whatman Filters. Preliminary results show that strong spatial patterns of floor dust loading (mg dust per square foot) can be observed for data aggregated at a spatial scale of about 1600 m (approximately 2.5 km2). Floor dust metal concentrations were similar to those found in other urban environments, with some regional variation. The median floor dust Pb concentration was approximately 108 mg x kg(-1) for this initial data set of approximately 264 sampled residential locations, and varied from 50 to 1100 mg Pb x kg(-1).

Air Pollution, Indoor↗

Phase II study of troxacitabine in chemotherapy-naive patients with advanced cancer of the pancreas: gastrointestinal tumors.

BACKGROUND: Troxacitabine (Troxatyl) is a novel L-enantiomer nucleoside analog with activity in pancreatic cancer xenograft models. PATIENTS AND METHODS: Troxacitabine 1.5 mg/m(2) was administered by 30-min infusions daily x5 every 4 weeks to 54 patients with advanced pancreatic cancer. Patients were evaluated for objective tumor response, time to tumor progression (TTP), changes in tumor marker CA 19-9, survival, safety, pain, analgesic consumption, Karnofsky performance status and weight change. RESULTS: Median TTP was 3.5 months (95% CI 2.0-3.8), median survival 5.6 months (95% CI 4.9-7.4), and the 1 year survival rate 19%. Best responses were stable disease in 24 patients with eight patients having stable disease for at least 6 months (15%). A 50% or greater decrease in CA 19-9 was seen in seven of 44 assessed patients (16%). Grade 3 and 4 neutropenia were observed in 37% and 30% of patients with one episode of febrile neutropenia. The most common drug-related non-hematological toxic effects reported were cutaneous, with 22% and 6% of patients reporting grade 2 and 3 skin rash, respectively and 4% grade 2 hand-foot syndrome. CONCLUSION: Troxacitabine administered by a bolus daily x5 monthly regimen has modest activity in advanced pancreatic adenocarcinoma.

Adult↗

Persistence of extracellular baculoviral DNA in aquatic microcosms: extraction, purification, and amplification by the polymerase chain reaction (PCR).

Genetically-modified baculoviruses have potential uses as bio-pesticides in forestry. However, the baculoviral occlusion bodies (OBs) may release genetically-modified DNA into the forest environment. In this research, outdoor aquatic microcosms, spiked with 673 microg of genomic DNA (4.4 x 10(12) target copies) from the genetically modified baculovirus Choristoneura fumiferana MNPVegt-/lacZ+, were exposed to natural summer conditions. A 530 bp DNA fragment from the genome of CfMNPVegt-/lacZ+ was detected in field microcosm water samples for about 24 h. The introduced DNA may have persisted for a longer time, but was below the detection limit of the PCR analysis (13.5 pg DNA or 8.9 x 10(4) target copies ml(-1) water). The detection limit of PCR was determined by spiking water samples with a dilution series of CfMNPVegt-/lacZ+ genomic DNA, extracting and purifying the DNA, and then PCR analysis. This study provides some of the first information on the persistence and detection limits of this viral DNA under aquatic ecological conditions, and the methods that can be used to conduct such a molecular-based field study.

Baculoviridae↗

Cytoplasmic membrane polarization in Gram-positive and Gram-negative bacteria grown in the absence and presence of tetracycline.

The ability of numerous diverse compounds and ions to cross the bacterial cytoplasmic membrane by diffusion and active transport is highly dependent on cytoplasmic membrane fluidity, which can be measured using fluorescent probes to estimate membrane polarization values. However, membrane polarization data are lacking for most bacterial species. The cytoplasmic membrane polarization values for Arthrobacter sp. ATCC 21908, Bacillus cereus NRC 3045, Pseudomonas fluorescens R2F, Pseudomonas putida NRC 2986 and Escherichia coli C600 bacterial cells were spectrofluorometrically measured over a temperature range from 10 to 50 degrees C, and in the absence and presence of 1 microg/ml tetracycline, using the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH) to obtain new information on their membrane fluidity. At an assay temperature of 10 degrees C, E. coli cells grown in the absence of tetracycline exhibited the highest cytoplasmic membrane polarization value (least fluid membrane) of 0.446, followed by values of 0.392, 0.371, 0.344 and 0.293, respectively, for B. cereus, Arthrobacter sp., P. fluorescens and P. putida. At an assay temperature of 30 degrees C, the polarization values ranged from 0.357 to 0.288 for cells grown in the absence of tetracycline, regardless of the species. B. cereus grown in the presence of 1 microg/ml tetracycline had lower polarization values than when grown in the absence of this antibiotic at all assay temperatures. Regardless of the absence or presence of 1 microg/ml tetracycline in the growth medium, all bacterial species generally exhibited a more fluid membrane as the assay temperature increased from 10 to 50 degrees C. To our knowledge, these are some of the first cytoplasmic membrane polarization values reported for these Gram-negative and Gram-positive bacteria over a broad temperature range and also for cells grown in the presence of tetracycline.

Cell Division↗

[Use of talc and sarcoidosis - pathogenic role of cutaneous talc exposure in sarcoidosis].

INTRODUCTION: We report on two patients with sarcoidosis with disseminated nodes, who used talc on irritated cutaneous areas. CASE REPORT: A histologic examination with intense polarised light showed up cristalline bi-refringent particles within vessels in contact with granulomatous areas. Microdissection followed by an electronic microscopy study and microanalysis was realised. In situ microanalysis allowed us to identify bi-refringent particles with a size of roughly 0.25microm as silica or silicate coming possibly from talc. We consequently studied a brand name talc. The diffraction spectrum showed that this product not only contained talc but also chlorite and quartz. Electron microscopy examination showed particles of all sizes even smaller than 0.25microm. These infra-microscopic particles, visible in a vessel only when agglomerated, could be invisible under optic microscopy (resolution: roughly 0.5microm) inside the granuloma even though they are responsible for it. Moreover, at this level of size of particles, they may escape mineralogic analyses which use methods involving the destruction of organic material, the mineral residue collecting on cellulose filter with a diameter generally of 0.45microm. CONCLUSION: Two recent epidemiologic studies confirm the possible role of mineral exposure in sarcoidosis. Some sarcoidosis could be caused by mineral overload on genetically predisposed patients. Some cases could be related to mineral powder application. Among different types of mineral exposure, applications of cosmetic products may induce disseminated granulomatous reaction on genetically predisposed patients. Such applications have to be considered in epidemiologic studies.

Adult↗

Persistence of isolated flow in the internal carotid artery in brain death.

The criteria for the confirmation of brain death (BD) using transcranial Doppler ultrasonography (TCD) state that flow should not be observed in the internal carotid artery (ICA). In 94 brain-dead patients examined by TCD, 19 (20%) had flow in the ICA despite cerebral circulatory arrest. There was no difference in the clinical characteristics of patients with or without isolated flow in the ICA. Shunting of blood from the ICA into the external carotid system or the arrest of blood flow at a higher level than the carotid siphon may explain our findings. Our results show that the current TCD criteria can result in a high rate of false negatives. We suggest that the TCD criteria for the diagnosis of brain death should be reviewed.

Adult↗

Enhanced interictal responsiveness of the migraineous visual cortex to incongruent bar stimulation: a functional MRI visual activation study.

Since visual aura is usually described as expanding zigzag lines, neurones involved with the perception of line orientation may initiate this phenomenon. A visual incongruent line stimulation protocol was developed to obtain functional magnetic resonance images (fMRI) interictally in 5 female migraine patients with typical fortification spectra and in 5 normal matched controls. Activation in the visual cortex was present contralateral to the side of stimulation in 4 of 5 patients, notably in the extrastriate visual cortex. In 4 of 5 controls activation was observed in the medial and anterior orbitofrontal cortex. In one of them additional activation at the right nucleus accumbens/ventral striatum and right ventral pallidum was present. In the remaining control subject activation was present in the left primary visual cortex. The enhanced interictal reactivity of the visual cortex in migraineurs supports the hypothesis of abnormal cortical excitability as an important pathophysiological mechanism in migraine aura, though the role of specific regions of the visual cortex remains to be explored.

Adult↗

Abrogation of protein convertase 2 activity results in delayed islet cell differentiation and maturation, increased alpha-cell proliferation, and islet neogenesis.

To date, the role of pancreatic hormones in pancreatic islet growth and differentiation is poorly understood. To address this issue, we examined mice with a disruption in the gene encoding prohormone convertase 2 (PC2). These mice are unable to process proglucagon, prosomatostatin, and other neuroendocrine precursors into mature hormones. Initiation of insulin (IN) expression during development was delayed in PC2 mutant mice. Cells containing IN were first detected in knockout embryos on d 15 of development, 5 d later than in wild-type littermates. However, the IN(+) cells of d 15 PC2 mutant mice coexpressed glucagon, as did the first appearing beta-cells of controls. In addition, lack of PC2 perturbed the pattern of expression of transcription factors presumed to be involved in the determination of the mature alpha-cell phenotype. Thus, in contrast to controls, alpha-cells of mutant mice had protracted expression of Nkx 6.1 and Pdx-1, but did not express Brn-4. Islets of adult mutant mice also contained cells coexpressing insulin and somatostatin, an immature cell type found only in islets of the wild-type strain during development. In addition to the effects on islet cell differentiation, the absence of PC2 activity resulted in a 3-fold increase in the rate of proliferation of proglucagon cells during the perinatal period. This increase contributed to the development of alpha-cell hyperplasia during postnatal life. Furthermore, the total beta-cell volume was increased 2-fold in adult mutants compared with controls. This increase was due to islet neogenesis, as the number of islets per section was significantly higher in knockout mice compared with wild-type mice, whereas both strains had similar rates of IN cell proliferation. These results indicate that hormones processed by PC2 affected processes that regulate islet cell differentiation and maturation in embryos and adults.

Age Factors↗

New large solar photocatalytic plant: set-up and preliminary results.

A European industrial consortium called SOLARDETOX has been created as the result of an EC-DGXII BRITE-EURAM-III-financed project on solar photocatalytic detoxification of water. The project objective was to develop a simple, efficient and commercially competitive water-treatment technology, based on compound parabolic collectors (CPCs) solar collectors and TiO2 photocatalysis, to make possible easy design and installation. The design, set-up and preliminary results of the main project deliverable, the first European industrial solar detoxification treatment plant, is presented. This plant has been designed for the batch treatment of 2 m3 of water with a 100 m2 collector-aperture area and aqueous aerated suspensions of polycrystalline TiO2 irradiated by sunlight. Fully automatic control reduces operation and maintenance manpower. Plant behaviour has been compared (using dichloroacetic acid and cyanide at 50 mg l(-1) initial concentration as model compounds) with the small CPC pilot plants installed at the Plataforma Solar de Almería several years ago. The first results with high-content cyanide (1 g l(-1)) waste water are presented and plant treatment capacity is calculated.

Automation↗

Efficacy, tolerability and management of raltitrexed (Tomudex) monotherapy in patients with advanced colorectal cancer. a review of phase II/III trials.

Raltitrexed (Tomudex), a thymidylate synthase inhibitor, is an alternative to 5-fluorouracil (5-FU)/leucovorin (LV) for the first-line treatment of advanced colorectal cancer. Following the completion of four phase III studies with raltitrexed at the recommended dose of 3.0 mg/m(2), it is opportune to review the efficacy and tolerability data of raltitrexed and suggest guidelines for appropriate patient management. Data are analysed from four phase III and five phase II studies including over 1300 patients with advanced colorectal cancer, some of whom were elderly or received higher doses of raltitrexed. Median survival with raltitrexed was comparable to that of bolus or infusional 5-FU/LV in three of the four randomised studies and objective response rates in the four trials were similar for the two agents. Response rates were at least comparable in elderly patients in phase II studies. For the majority of patients, treatment with raltitrexed was well tolerated even at doses higher than that recommended or in the elderly. As with other cytotoxic agents, serious and potentially life-threatening side-effects can occur; nevertheless, adherence to simple patient guidelines should minimise the incidence of serious side-effects with raltitrexed; these include the assessment of renal function before each and every treatment, dosage adjustment in the presence of renal impairment and close monitoring with prompt treatment of toxicities, particularly diarrhoea and neutropenia.

Adult↗

[Clinical implications of blood pressure variability].

There are many variations in blood pressure, ranging from that observed between systole and diastole (pulse pressure) to slower daily or seasonal variations. This variability has many facets, for example the simple concept of variation around the mean blood pressure and the more complex spectral, chaos or fractal analysis... Some of these concepts are still the subject of fundamental research and have no current clinical applications. Others, however, are already part of our evaluation of hypertensive patients or used as prognostic factors in cardiac failure or myocardial infarction. Blood pressure variability, either the pulse pressure or 24 hour variability, is associated with a higher incidence of cardiovascular complications. Although the causality of the relationship is uncertain, patients with the greatest variability seem to be at higher risk. In addition to this prognostic impact, the study of changes in blood pressure by spectral analysis may also provide indices of adrenergic tone or sympathovagal equilibrium which may be useful clinically. Finally, the combined study of blood pressure variability and heart rate lead to the baroreflex, the sensitivity of which integrates major risk factors such as blood pressure, age, heart rate and serum cholesterol. This baroreflex could be a useful parameter for stratification of cardiovascular risk. This has already been demonstrated in patients at high risk, such as those with cardiac failure or myocardial infarction.

Baroreflex↗

Phase II study of carboplatin and liposomal doxorubicin in patients with recurrent squamous cell carcinoma of the cervix.

BACKGROUND: The activity of the combination of carboplatin and liposomal doxorubicin was tested in a Phase II study of patients with recurrent cervical carcinoma. METHODS: The combination of carboplatin (area under the concentration curve [AUC], 5) and liposomal doxorubicin (Doxil; starting dose, 40 mg/m(2)) was administered intravenously every 28 days to 37 patients with recurrent squamous cell cervical carcinoma to determine antitumor activity and toxicity profile. RESULTS: Twenty-nine patients were assessable for response, and 35 patients were assessable for toxicity. The overall response rate was 38%, the median time to response was 10 weeks, the median duration of response was 26 weeks, and the median survival was 37 weeks. The main toxic effect was myelosuppression, with Grade 3 and 4 neutropenia in 16 patients, anemia in 12 patients, thrombocytopenia in 11 patients, and neutropenic fever in 3 patients. Four patients had five infusion-related reactions during the infusion of liposomal doxorubicin, leading to treatment discontinuation in three patients. Grade > or = 2 nonhematologic toxicity included nausea in 17 patients, emesis in 14 patients, fatigue in 9 patients, mucositis and/or stomatitis in 8 patients, constipation in 6 patients, weight loss in 5 patients, hand-foot syndrome in 2 patients, and skin reactions in 3 patients. CONCLUSIONS: The combination of carboplatin and liposomal doxorubicin has modest activity in patients with recurrent cervical carcinoma.

Adult↗

Dopamine and glutamate induce distinct striatal splice forms of Ania-6, an RNA polymerase II-associated cyclin.

Control of neuronal gene expression by drugs or neurotransmitters is a critical step in long-term neural plasticity. Here, we show that a gene induced in the striatum by cocaine or direct dopamine stimulation, ania-6, is a member of a novel family of cyclins with homology to cyclins K/T/H/C. Further, different types of neurotransmitter stimulation cause selective induction of distinct ania-6 isoforms, through alternative splicing. The longer Ania-6 protein colocalizes with nuclear speckles and is associated with key elements of the RNA elongation/processing complex, including the hyperphosphorylated form of RNA polymerase II, the splicing factor SC-35, and the p110 PITSLRE cyclin-dependent kinase. Distinct types of neuronal stimulation may therefore differentially modulate nuclear RNA processing, through altered transcription and splicing of ania-6.

Alternative Splicing↗

Molecular polymorphism of the intermediate filament protein transitin.

Transitin is an avian intermediate filament protein whose transient expression in the progenitor cells of the muscle and nerve tissues is similar to that of mammalian nestin. Both proteins contain an alpha-helical core domain flanked by a short N-terminal head and a long C-terminal extremity. However, the tail region of transitin is significantly different from that of nestin in that it harbors a unique motif containing more than 50 leucine zipper-like heptad repeats which is not found in any other intermediate filament protein. Despite the absence of introns in this region of the transitin gene, it was reported that different isoforms of the protein were produced by exclusion or inclusion of a number of repeats generated by an unusual splicing mechanism recognizing consensus 5' and 3' splice sites contained within the coding sequence of the heptad repeat domain [Napier et al. (1999) J Mol Neurosci 12:11-22]. Two monoclonal antibodies (mAbs) reacting with repeated epitopes of this motif were used to monitor transitin expression during in vitro myogenesis of the quail myogenic cell line QM7. Confocal microscopy revealed that the subcellular domains decorated with mAbs A2B11 and VAP-5 were mutually exclusive: the intermediate filament network visualized with mAb VAP-5 appeared to abut on a submembranous domain defined by mAb A2B11. When QM7 cells were induced to differentiate by switching to medium containing low serum components, an early effect was the local loss of A2B11 cortical staining at the points of cell-cell contacts. The A2B11 signal also disappeared before that of VAP-5 in newly formed myotubes. Unexpectedly, the mutually exclusive staining pattern of the mAbs could not be explained by alternative splicing since both epitopes mapped to a repeated element preceding the consensus 5' splice sites of the heptad repeat domain. An alternative explanation would be that the central repeat domain of transitin is a polymorphic structure from which different conformations exist depending on the local context. This hypothesis is strengthened by the observation that in cultured neural crest cells, the A2B11 antigen is preferentially expressed by freely migrating crest cells whose intracellular pH and calcium concentrations are different from those of non-migrating cells.

Amino Acid Sequence↗