Biomedical subjects

M Poirier

Publications and source records attributed to M Poirier.

At least 19 recordsLinked to original sources

PubMed2007

Malone antegrade continent enema: an alternative to resection in severe defecation disorders.

PURPOSE: This study was designed to evaluate patient self-reported outcome of the Malone antegrade continent enema at a single institution in patients suffering from severe defecatory disorders. METHODS: A total of 18 patients (15 females; median age, 31 (range, 12-63) years) underwent a Malone antegrade continent enema (August 1999 to September 2004). The Malone antegrade continent enema technique has been previously described; however, in this series emphasis was placed on method appendix tunneling. Patients' charts were reviewed and follow-up telephone interviews were conducted. Indications for Malone antegrade continent enema were chronic constipation (n = 12), intractable fecal incontinence (n = 5), or both (n = 1). The underlying pathology included neurogenic (n = 2), congenital (n = 4), postsurgery-related (n = 4), irritable bowel syndrome (n = 6), and megarectum (n = 2). The appendix (n = 17) or cecum (n = 1) was used as a conduit. RESULTS: The mean follow-up was 18.5 (range, 3-67) months. Fourteen patients (78 percent) still use the Malone antegrade continent enema routinely and report good functional outcome. Three patients (20 percent) required stoma creation as subsequent alternate treatment. A total of 10 patients experienced 12 complications: 3 perioperative (infections) and 9 postoperative Malone antegrade continent enema use/nonuse complications (4 stomal orifice strictures, 2 fecal impactions, 2 appendiceal perforations, and 1 irrigation catheter knot). No patient experienced leakage from the appendiceal stoma. During the follow-up interval, one patient underwent proctectomy for megarectum. No failures occurred in patients with congenital or neurogenic disorders. CONCLUSIONS: Malone antegrade continent enema is a reasonable option for the treatment of select patients with severe defecation disorders. Good functional patient self-reported outcome was achieved by 78 percent of patients. The social inconvenience of stoma leakage is avoided with appropriate surgical technique. Malone antegrade continent enema is one option that provides a less invasive surgical alternative than colectomy or ileostomy for severe defecation disorders.

Adolescent↗

PubMed2006

First order phase transition in the frustrated triangular antiferromagnet CsNiCl3.

By means of high-resolution ultrasonic velocity measurements, as a function of temperature and magnetic field, the nature of the different low temperatures magnetic phase transitions observed for the quasi-one-dimensional compound CsNiCl3 is established. Special attention has been devoted to the field-induced 120 degrees phase transition above the multicritical point in the H-T phase diagram where the elastic constant C44 reveals a steplike variation and hysteresis effects. These results represent the first experimental evidence that the 120 degrees phase transition is weakly first order and contradict the popular notion of new universality classes for chiral systems.

Journal Article↗

PubMed2006

Peak anaerobic power in patients with COPD: gender related differences.

The aim of the study was to investigate peak anaerobic power during all-out exercise in patients with COPD. Twenty patients (ten women, ten men) [FEV1=50.5 (7.6)% of predicted] and 11 healthy subjects (six women, five men) performed: (1) three maximal sprints on a cycle ergometer to measure peak anaerobic power (Pmax) and optimal velocity (Vopt), (2) assessment of whole-body composition by dual-energy X-ray absorptiometry (DEXA) and (3) assessment of mean habitual daily energy expenditure (MHDEE). Pmax was 30% lower in COPD than in healthy subjects [22.9 (7.1) vs. 32.8 (5.6) W kg-1 (legs FFM), P<0.001]. Nevertheless, Vopt was similar in both series. In COPD, Pmax was lower in women than in men [21.4 (7.7) vs. 23.8(6.4) W kg-1 (legs FFM), P<0.05]. Vopt was lower in women than in COPD men [72.6 (11.3) vs. 89.3 (13.8) rpm, P<0.05]. MHDEE was lower in COPD than in healthy subjects [8019 (1254) vs. 9093 (1660) kJ day-1]. In COPD, MHDEE was lower in women than in men (P<0.001). This study demonstrates that in COPD patients, the decrease in peak anaerobic power could play a role in their specific muscular dysfunction. Considerable differences were observed in peripheral muscle function, body composition and MHDEE between women and men. The skeletal muscle of women and men may therefore adapt to COPD in different ways.

Aged↗

PubMed2003

Mott transition, compressibility divergence, and the P-T phase diagram of layered organic superconductors: an ultrasonic investigation.

The phase diagram of the organic superconductor kappa-(BEDT-TTF)(2)Cu[N(CN)(2)]Cl has been investigated by ultrasonic velocity measurements under helium gas pressure. Different phase transitions were identified through several elastic anomalies characterized from isobaric and isothermal sweeps. Our data reveal two crossover lines that end on the critical point terminating the first-order Mott transition line. When the critical point is approached along these lines, we observe a dramatic anomaly of the sound velocity which is consistent with a diverging compressibility of the electronic degrees of freedom.

Journal Article↗

PubMed2001

An anion-induced regio- and chemoselective acylation and its application to the synthesis of an anticancer agent.

[reaction--see text] An efficient Grignard- and organolithium-induced regio- and chemoselective anionic acylation is reported. A number of tricyclic ketones are prepared in good to excellent yields via this method. This method is complementary to the Frieldel-Crafts acylation for electron-deficient substrates. A novel anisole-based Grignard reagent was developed to effect the cyclization of sterically hindered substrates. This novel reagent has been successfully applied to the synthesis of Sch 66336, a candidate for oncologic treatment.

Acylation↗

PubMed2001

Nonpeptidic, monocharged, cell permeable ligands for the p56lck SH2 domain.

p56lck is a member of the src family of tyrosine kinases and plays a critical role in the signal transduction events that lead to T cell activation. Ligands for the p56lck SH2 domain have the potential to disrupt the interaction of p56lck with its substrates and derail the signaling cascade that leads to the production of cytokines such as interleukin-2. Starting from the quintuply charged (at physiological pH) phosphorylated tetrapeptide, AcpYEEI, we recently disclosed (J. Med. Chem. 1999, 42, 722 and J. Med. Chem. 1999, 42, 1757) the design of the modified dipeptide 3, which carries just two charges at physiological pH. Here we present the elaboration of 3 to the nonpeptidic, monocharged compound, 9S. This molecule displays good binding affinity for the p56lck SH2 domain (K(d) 1 microM) and good cell permeation, and this combination of properties allowed us to demonstrate clear-cut inhibitory effects on a very early event in T cell activation, namely calcium mobilization.

Caco-2 Cells↗

PubMed2001

Solid-phase synthesis of peptidomimetic inhibitors for the hepatitis C virus NS3 protease.

The NS3 serine protease enzyme of the hepatitis C virus (HCV) is essential for viral replication. Short peptides mimicking the N-terminal substrate cleavage products of the NS3 protease are known to act as weak inhibitors of the enzyme and have been used as templates for the design of peptidomimetic inhibitors. Automated solid-phase synthesis of a small library of compounds based on such a peptidomimetic scaffold has led to the identification of potent and highly selective inhibitors of the NS3 protease enzyme.

Combinatorial Chemistry Techniques↗

PubMed2001

Endovascular treatment of occlusive lesions in the distal aorta: mid-term results in a series of 31 consecutive patients.

The purpose of this study was to evaluate the early and mid-term results of endovascular treatment of occlusive lesions in the distal aorta in a consecutive series of patients. Between February 1996 and March 1999, a total of 31 patients underwent transluminal procedures for treatment of occlusive atherosclerotic lesions located at the lower end of the aorta. Thirty patients presented with intermittent claudication and one had critical ischemia. Manifestations were bilateral in 26 cases and unilateral in 5. The lesion was confined to the lower aorta in 3 patients and extended to the common iliac arteries in 19, with predominant proximal lesions of the common iliac artery occurring in 9 patients. Fourteen patients had concurrent infracrural occlusive lesions. All patients underwent exclusive endovascular treatment without any associated open surgical procedure. The three patients with isolated aortic lesions were treated by angioplasty, followed by stent placement in two cases. The 19 patients with aortobiiliac lesions were treated by bilateral common iliac artery angioplasty according to the "kissing-balloon" technique; 7 of these patients also underwent aortic angioplasty. In these 19 patients, aortic stenting was performed in 3 cases and bilateral iliac stenting in 10 cases, including 3 in association with aortic stenting. The nine patients with a proximal lesion of the common iliac arteries were treated by angioplasty, followed by bilateral stenting in three cases and unilateral stenting in three cases. The findings of this study show that the mid-term anatomical and functional results of endovascular treatment for atherosclerotic lesions of the distal aorta are satisfactory. We recommend it as the initial treatment modality.

Adult↗

PubMed2000

Highly potent and selective peptide-based inhibitors of the hepatitis C virus serine protease: towards smaller inhibitors.

Structure-activity studies on a hexapeptide N-terminal cleavage product of a dodecamer substrate led to the identification of very potent and highly specific inhibitors of the HCV NS3 protease/NS4A cofactor peptide complex. The largest increase in potency was accomplished by the introduction of a (4R)-naphthalen-1-yl-4-methoxy substituent to the P2 proline. N-Terminal truncation resulted in tetrapeptides containing a C-terminal carboxylic acid, which exhibited low micromolar activity against the HCV serine protease.

Animals↗

PubMed2000

Reversible and irreversible unfolding of mitotic newt chromosomes by applied force.

The force-extension behavior of individual mitotic newt chromosomes was studied, using micropipette surgery and manipulation, for elongations up to 80 times native length. After elongations up to five times, chromosomes return to their native length. In this regime chromosomes have linear elasticity, requiring approximately 1 nN of force to be stretched to two times native length. After more than five times stretching, chromosomes are permanently elongated, with force hysteresis during relaxation. If a chromosome is repeatedly stretched to approximately 10 times native length and relaxed, a series of hysteresis loops are obtained that converge to a single reversible elastic response. For further elongations, the linear dependence of force on extension terminates at a force "plateau" of approximately 15-20 nN, near 30 times extension. After >30 times extensions, the elastic moduli of chromosomes can be reduced by more than 20-fold, and they appear as "ghosts": swollen, elongated, and with reduced optical contrast under both phase and differential interference contrast imaging. Antibody labeling indicates that histone proteins are not being lost during even extreme extensions. Results are interpreted in terms of extension and failure of chromatin-tethering elements; the force data allow estimates of the number and size of such connectors in a chromosome.

Animals↗

PubMed2000

Citrate release by perfused rat hearts: a window on mitochondrial cataplerosis.

Cytosolic citrate is proposed to play a crucial role in substrate fuel selection in the heart. However, little is known about factors regulating the transfer of citrate from the mitochondria, where it is synthesized, to the cytosol. Further to our observation that rat hearts perfused under normoxia release citrate whose (13)C labeling pattern reflects that of mitochondrial citrate (B. Comte, G. Vincent, B. Bouchard, and C. Des Rosiers. J. Biol. Chem. 272: 26117-26124, 1997), we report here data indicating that this citrate release is a specific process reflecting the mitochondrial efflux of citrate, a process referred to as cataplerosis. Indeed, measured rates of citrate release, which vary between 2 and 21 nmol/min, are modulated by the nature and concentration of exogenous substrates feeding acetyl-CoA (fatty acid) and oxaloacetate (lactate plus pyruvate) for the mitochondrial citrate synthase reaction. Such release rates that represent at most 2% of the citric acid cycle flux are in agreement with the activity of the mitochondrial tricarboxylate transporter whose participation is also substantiated by 1) parallel variations in citrate release rates and tissue levels of citrate plus malate, the antiporter, and 2) a lowering of the citrate release rate by 1,2, 3-benzenetricarboxylic acid, a specific inhibitor of the transporter. Taken together, the results from the present study indicate that citrate cataplerosis is modulated by substrate supply, in agreement with the role of cytosolic citrate in fuel partitioning, and occurs, at least in part, through the mitochondrial tricarboxylate transporter.

Acetyl Coenzyme A↗

PubMed2000

Immediate serial recall of words and nonwords: tests of the retrieval-based hypothesis.

In two experiments, the immediate serial recall of lists of words or nonwords was investigated under quiet and articulatory suppression conditions. The results showed better item recall for words but better order recall for nonwords, as measured with proportion of order errors per item recalled. Articulatory suppression hindered the recall of item information for both types of lists and of order information for words. These results are interpreted in light of a retrieval account in which degraded phonological traces must undergo a reconstruction process calling on long-term knowledge of the to-be-remembered items. The minimal long-term representations for nonwords are thought to be responsible for their lower item recall and their better order recall. Under suppression, phonological representations are thought to be minimal, producing trace interpretation problems responsible for the greater number of item and order errors, relative to quiet conditions. The very low performance for nonwords under suppression is attributed to the combination of degraded phonological information and minimal long-term knowledge.

Adult↗

PubMed1999

Novel 2,2-bipyridine ligand for palladium-catalyzed regioselective carbonylation.

[reaction: see text] A palladium-catalyzed highly regioselective one-step carbonylation of 2,5-dibromo-3-methylpyridine is reported. A range of alkyl esters and amides can be prepared in good yield with better than 95:5 regioselectivity via this method. Key to the high regioselectivity for the formation aromatic amides is the introduction of a novel nonphosphine-based 2,2-bipyridine ligand. This novel reaction was scaled up smoothly in the plant to a 130-kg batch size and facilitated the delivery of bulk material for the clinical trials of Sch 66336, a candidate for oncologic treatments.

Antineoplastic Agents↗

PubMed1999

Ligands for the tyrosine kinase p56lck SH2 domain: discovery of potent dipeptide derivatives with monocharged, nonhydrolyzable phosphate replacements.

p56lck is a member of the src family of tyrosine kinases. Through modular binding units called SH2 domains, p56lck promotes phosphotyrosine-dependent protein-protein interactions and plays a critical role in signal transduction events that lead to T-cell activation. Starting from the phosphorylated dipeptide (2), a high-affinity ligand for the p56lck SH2 domain, we have designed novel dipeptides that contain monocharged, nonhydrolyzable phosphate group replacements and bind to the protein with KD's in the low micromolar range. Replacement of the phosphate group in phosphotyrosine-containing sequences by a (R/S)-hydroxyacetic (compound 8) or an oxamic acid (compound 10) moiety leads to hydrolytically stable, monocharged ligands, with 83- and 233-fold decreases in potency, respectively. This loss in binding affinity can be partially compensated for by incorporating large lipophilic groups at the inhibitor N-terminus. These groups provide up to 13-fold increases in potency depending on the nature of the phosphate replacement. The discovery of potent (2-3 microM), hydrolytically stable dipeptide derivatives, bearing only two charges at physiological pH, represents a significant step toward the discovery of compounds with cellular activity and the development of novel therapeutics for conditions associated with undesired T-cell proliferation.

Crystallography, X-Ray↗

PubMed1999

Phosphotyrosine-containing dipeptides as high-affinity ligands for the p56lck SH2 domain.

Src homology-2 (SH2) domains are noncatalytic motifs containing approximately 100 amino acid residues that are involved in intracellular signal transduction. The phosphotyrosine-containing tetrapeptide Ac-pYEEI binds to the SH2 domain of p56lck (Lck) with an affinity of 0.1 microM. Starting from Ac-pYEEI, we have designed potent antagonists of the Lck SH2 domain which are reduced in peptidic character and in which the three carboxyl groups have been eliminated. The two C-terminal amino acids (EI) have been replaced by benzylamine derivatives and the pY + 1 glutamic acid has been substituted with leucine. The best C-terminal fragment identified, (S)-1-(4-isopropylphenyl)ethylamine, binds to the Lck SH2 domain better than the C-terminal dipeptide EI. Molecular modeling suggests that the substituents at the 4-position of the phenyl ring occupy the pY + 3 lipophilic pocket in the SH2 domain originally occupied by the isoleucine side chain. This new series of phosphotyrosine-containing dipeptides binds to the Lck SH2 domain with potencies comparable to that of tetrapeptide 1.

Binding, Competitive↗

PubMed1999

Semantic similarity and immediate serial recall: is there a detrimental effect on order information?

Four experiments investigated the disruptive effect of semantic similarity on short-term ordered recall. Experiments 1 and 2 contrasted immediate serial recall performance for lists of semantically similar items, drawn from the same semantic category, with performance for lists that contained items from different categories. Experiments 1 and 2 showed the usual similarity advantage for item information recall, but, contrary to expectations, there was no similarity disadvantage for the recall of order information even when the level of item recall was controlled. Experiments 3 and 4 replicate and extend these findings by using an order reconstruction task or a limited word pool strategy, both of which yield alternate measures of order retention. These findings clearly contradict the wide spread belief stating that semantic similarity hinders the short-term recall of order information. Results are discussed in the light of a retrieval-based account where the effects of semantic similarity reflect the processes called upon at recall: It is suggested that long-term knowledge is accessed to support the interpretation of degraded phonological traces.

Adult↗

PubMed1999

[Splendor and misery in the local organization of mental health: a look at the field].

Collaboration among public and community resources (or concentration as it is referred to in French) is a practice much favoured by governments for ideological and economic reasons. But if administrative collaboration is relatively easy to set up, what about collaboration among front-line field workers? What are the ingredients likely to engender true collaboration among practitioners, and what obstacles do they meet with on a practical day-to-day level? Experience acquired in the West Island area of greater Montreal has led us to the conclusion that many issues need to be examined and understood: the difficulty of reconciling client empowerment with treatment; the difficulty of harmonizing the values and convictions prevailing in institutional and community-based networks; the tendency for practitioners to keep clienteles for themselves within a treatment environment. Despite these difficulties, it is evident that there will be a trend towards increasing collaboration where clienteles are growing and where problems are becoming more complex.

Community Mental Health Services↗

PubMed1998

Studies on the C-terminal of hexapeptide inhibitors of the hepatitis C virus serine protease.

Replacement of the C-terminal carboxylic acid functionality of peptide inhibitors of hepatitis C virus (HCV) NS3 protease (complexed with NS4A peptide cofactor) by activated carbonyl groups does not produce any substantial increase in potency. These latter inhibitors also inhibit a variety of other serine and cysteine proteases whereas the carboxylic acids are specific. Norvaline was identified as a chemically stable replacement for the P1 residue of Ac-DDIVPC-OH which was also compatible with activated carbonyl functionalities.

Cysteine↗