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Biomedical subjects

P Beaulieu

Publications and source records attributed to P Beaulieu.

At least 19 recordsLinked to original sources
PubMed1999

Descriptive study to compare patient recall of information: nurse-taught versus video supplement.

An important goal in oncology nursing is to provide outpatients receiving chemotherapy with adequate information about their treatment so they will be able to cope with treatment reactions and make appropriate decisions about seeking early medical attention when potentially serious side-effects occur. The purpose of the present study was to evaluate patient teaching strategies at one cancer centre. A comparative descriptive study design was employed. A group of patients receiving one-to-one nurse/patient teaching was compared to a group of patients receiving one-to-one nurse/patient teaching plus a take-home instructional chemotherapy video. The patient groups were compared with respect to: a) level of recall of chemotherapy information; b) the sources of information used; and c) preferred information sources. When the mean scores achieved on the chemotherapy knowledge questionnaire were compared, no statistically significant differences were found between the two groups. In fact, both groups showed a "high" level of information recall. Both patient groups reported using a variety of information sources to learn about their chemotherapy, however, for both groups the preferred sources of information were their direct health care providers. The results of the study raise interesting issues about the feasibility of developing "high-tech" patient education strategies.

Adolescent↗
PubMed1998

Peptidic regulation of heart rate and interactions with the autonomic nervous system.

Autonomic influences on the heart rate have been the subject of intense research for many decades and are classically devoted to the sympathetic and parasympathetic systems. However, developments over the past few years in our knowledge of the organization of the autonomic nervous system have led to the conclusion that in addition to the classical transmitters, peptidic transmitters are clearly present and have direct or indirect actions on cardiac conduction. Neuropeptides have been found to collocate with each other or with classical transmitters, thereby increasing the variety of chemical signals that a neuron can utilize to communicate with other cells. Neuropeptides can act as neurotransmitters, neuromodulators or neurohormones. Some are produced in endocrine glands and circulate as hormones, while others are contained in cardiac myocytes, neurons, or endothelial cells in proximity to the sinoatrial node and can therefore act in a paracrine or autocrine way on the pacemaker cells to modulate heart frequency. There is evidence supporting such a role, especially for locally situated neuropeptide Y, vasoactive intestinal peptide, calcitonin gene-related peptide, substance P, angiotensin II, natriuretic peptides, endothelins and possibly many others. The role of the peptidic neurotransmitters in the conduction system should not be exaggerated. Nevertheless, neuropeptides certainly represent a new category of neurotransmitters forming a third component of the autonomic nervous system and may have complex actions with potential therapeutic implications in man.

Autonomic Nervous System↗
PubMed1997

Positive chronotropic and inotropic effects of C-type natriuretic peptide in dogs.

We have recently reported that C-type natriuretic peptide (CNP) has a positive chronotropic effect in dogs. We further investigated the effect of CNP on canine cardiac functions: 1) in situ, by exploring the effects of isoproterenol (10 microg), angiotensin II (ANG II, 5 microg), and CNP (40 microg) injections (n = 8) on computerized epicardial mapping of atrial activation to detect a shift in pacemaker location; 2) by examining the presence of natriuretic peptide receptor (NPR)-A and -B mRNAs in atrial and nodal tissues using semiquantitative reverse-transcription polymerase chain reaction; 3) in vitro, using spontaneously beating right atrial preparations (n = 6), by recording the transmembrane potentials of sinoatrial node (SAN) cells before and after injection of CNP (25 microg); and 4) by observing the effects of CNP (25 microg) on contractile force of paced isolated right atrial preparations (n = 6). The results indicate that 1) the site of earliest extracellular electrical activation in the SAN remains mostly unchanged in response to CNP, whereas it shifts to the superior region of the SAN after isoproterenol and ANG II injections; 2) NPR-A and -B mRNAs are present in atrial and nodal tissues; 3) CNP significantly increases the maximal rate of diastolic depolarization and decreases the action potential duration at 75 and 90% of repolarization; and 4) CNP significantly increases atrial contractile force. These results suggest that CNP modifies cardiac ionic currents to produce positive chronotropic and inotropic effects by stimulation of NPR-B receptors, located in the SAN region, and that CNP plays a role in the modulation of cardiac function.

Action Potentials↗
PubMed1996

Peptidomimetic inhibitors of herpes simplex virus ribonucleotide reductase with improved in vivo antiviral activity.

We have been investigating the potential of a new class of antiviral compounds. These peptidomimetic derivatives prevent association of the two subunits of herpes simplex virus (HSV) ribonucleotide reductase (RR), an enzyme necessary for efficient replication of viral DNA. The compounds disclosed in this paper build on our previously published work. Structure-activity studies reveal beneficial modifications that result in improved antiviral potency in cell culture in a murine ocular model of HSV-induced keratitis. These modifications include a stereochemically defined (2,6-dimethylcyclohexyl)amino N-terminus, two ketomethylene amide bond isosteres, and a (1-ethylneopentyl)amino C-terminus. These three modifications led to the preparation of BILD 1351, our most potent antiherpetic agent containing a ureido N-terminus. Incorporation of the C-terminal modification into our inhibitor series based on a (phenylpropionyl)valine N-terminus provided BILD 1357, a significantly more potent antiviral compound than our previously published best compound, BILD 1263.

Animals↗
PubMed1996

Ureido-based peptidomimetic inhibitor of herpes simplex virus ribonucleotide reductase: an investigation of inhibitor bioactive conformation.

We have been investigating peptidomimetic inhibitors of herpes simplex virus (HSV) ribonucleotide reductase (RR). These inhibitors bind to the HSV RR large subunit and consequently prevent subunit association and subsequent enzymatic activity. This report introduces a new series of compounds that contain an extra nitrogen (a ureido function) at the inhibitor N-terminus. This nitrogen improves inhibitor binding potency 50-fold over our first published inhibitor series. Evidence supports that this improvement in potency results from a new hydrogen-bonding contact between the inhibitor and the RR large subunit. This report also provides evidence for the bioactive conformation around two important amino acid residues contained in our inhibitors. A tert-butyl group, which contributes 100-fold to inhibitor potency but does not directly bind to the large subunit, favors an extended beta-strand conformation that is prevalent in solution and in the bound state. More significantly, the bioactive conformation around a pyrrolidine-modified asparagine residue, which contributes over 30 000-fold to inhibitor potency, is elucidated through a series of conformationally restricted analogues.

Enzyme Inhibitors↗
PubMed1996

Patient-controlled analgesia after spinal fusion for idiopathic scoliosis.

One hundred adolescents undergoing posterior spinal fusion for scoliosis were reviewed to assess the adequacy of postoperative patient-controlled analgesia. There were 94 females and 6 males. The mean settings for morphine dosage were a loading dose of 114.5 micrograms.kg-1, a bolus dose of 24.8 micrograms.kg-1, and a lockout interval of 9.9 minutes. This was used for an average of 75.8 h, with a 52.2% success rate. Adolescents using patient-controlled analgesia showed a great variability in morphine requirements with greater use as they became older. The requirement was not significantly different on the 1st, 2nd and 3rd postoperative days and the total consumption was 52.2 micrograms.kg-1.h-1. Nausea and vomiting occurred in 45% and pruritus in 15%. There were 7 cases of respiratory depression who all recovered promptly and completely. This method is associated with high morphine requirements in adolescents, but can be used safely.

Adolescent↗
PubMed1996

[Incontinentia pigmenti].

Incontinentia pigmenti (IP) is a hereditary syndrome characterized by specific skin lesions occurring mostly during the neonatal period (96% of the cases before 6 weeks of age). These skin lesions have four steps of evolution: inflammatory or erythemato-bullous stage (very often associated with peripheral blood hyper-eosinophilia), proliferative or verruco-lichenoid stage, pigmentary or terminal stage characterized by "fountain" or "firework" features (with a picture of pigmentary incontinence at histological examination), sometimes there is a fourth stage referred to as "involutive". Ocular and neurological involvement is the main determinant in the prognosis. Eye lesions include corneal flecks, cataracts, uveitis or optical atrophy with retrolental fribroplasia. The neurological involvement includes pyramidal syndrome, cerebral ataxia, microcephalia, and mental retardation. The disease has mainly an X-linked dominant transmission and is usually lethal for males. Rare cases are observed in boys, some being associated with Klinefelter syndrome. Research is ongoing to identify the IP gene on the X chromosome. In the family form of IP, the gene has been located on chromosome Xq28, which allows prenatal diagnosis using trophoblast biopsy.

Eye Diseases↗
PubMed1996

Direct chronotropic effects of atrial and C-type natriuretic peptides in anaesthetized dogs.

1. The chronotropic effects of atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP) were investigated using injections (50 micrograms in 1 ml of Tyrode solution as bolus over 1 min) directly into the sinus node artery of 21 anaesthetized and vagotomized dogs which had been pretreated with a beta-adrenoceptor antagonist. The injections were also repeated following: (a) alpha-adrenoceptor antagonism (prazosin) and muscarinic receptor antagonism (atropine); (b) inhibition of prostaglandin synthesis (indomethacin); (c) angiotensin II AT1 receptor antagonism (losartan); (d) histamine H1 (mepyramine) and H2 (cimetidine) receptor antagonism. 2. The results obtained indicate that ANP had no significant effect on the basal sinus rate, whereas CNP produced a slight but significant increase of 12 +/- 2 beats min-1. The effect of CNP was long-lasting (return to pre-injection levels after maximum effect in 17 +/- 3 min) and was not influenced by the various antagonists mentioned above. 3. During in vitro experiments on spontaneously beating right atria isolated from 6 dogs, the injection of CNP (50 micrograms in 1 ml of Tyrode solution) into the sinus node artery produced an increase in atrial rate of 14 +/- 1 beats min-1. 4. The results of this work indicate that CNP exerts a significant and prolonged positive chronotropic effect both in vivo and in vitro. Other studies are required to elucidate the mechanism of action of CNP on the heart conduction system, to ascertain the presence of natriuretic peptide receptor B in the region of the sinoatrial node and to determine the role of CNP in the control of heart rate.

Adrenergic beta-Antagonists↗
PubMed1996

Latex anaphylaxis in a myasthenic child undergoing thymectomy.

Anaphylactic shock occurred in a 9-year-old myasthenic boy after induction of anesthesia for thymectomy. Resuscitation was successful. Subsequent skin testing identified latex as the cause. Although the patient was not in a high-risk group for latex allergy, detailed questioning confirmed that sensitivity had developed during repeated exposures in previous anesthesia and dental care. Six months later, after taking steroids and antihistaminic drugs prophylactically and avoiding all latex-containing products, the boy underwent uncomplicated thymectomy. The possibility of latex allergy should be borne in mind when dealing with patients previously exposed to repeated medical care. Adequate, latex-free equipment should be available in operating rooms to deal with patients who are allergic to latex.

Anaphylaxis↗
PubMed1995

Peptidomimetic inhibitors of herpes simplex virus ribonucleotide reductase: a new class of antiviral agents.

We have been investigating a new class of antiviral compounds effective against herpes simplex virus (HSV) in vitro and in vivo. Antiviral activity results from inhibition of HSV ribonucleotide reductase (RR). The inhibitors are designed as mimics of the RR small subunit C-terminus, a region essential for RR subunit association and consequently enzymatic activity. Inhibition results from specific binding of the inhibitor to the HSV RR large subunit thereby preventing subunit association. This report details the structure--activity studies that lead to the indentification of BILD 1263, a potent inhibitor of HSV RR subunit association (IC50, 0.2 nM) that also inhibits the replication of HSV types 1 and 2 in cell culture (EC50, 3 and 4 microM) and reduces the severity of HSV-1-induced keratitis in a murine ocular model. The discovery of inhibitors with in vitro antiviral results from a combination of improving inhibitor potency in a RR binding assay and modifying inhibitor physicochemical properties. The importance and possible role of the new structural modifications introduced into this inhibitor series is discussed.

Animals↗