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Biomedical subjects

S Laplante

Publications and source records attributed to S Laplante.

17 recordsLinked to original sources
PubMed2000

Circumstances leading to a change to prone sleeping in sudden infant death syndrome victims.

CONTEXT: In addition to usual prone sleeping, unaccustomed prone sleeping represents a significant risk factor for sudden infant death syndrome (SIDS). However, little information is available regarding the circumstances leading caretakers to change the infant's sleep position to prone position in SIDS victims. OBJECTIVE: To determine, in a population of SIDS victims, the timing of a change to prone sleeping and the reason for that change in infants who were originally nonprone sleepers. DESIGN AND SETTING: Case series analysis from a questionnaire administered between 1991 and 1997 to parents and other caretakers of SIDS victims in the province of Quebec (Canada). SUBJECTS: One hundred fifty-seven SIDS cases occurring in the province during the study. RESULTS: Of the 157 SIDS cases studied, 139 were found in the prone position, although only 93 infants usually slept prone. Of the 64 nonprone sleepers, 34 had been changed to prone by the parents or another caretaker before death, and 18 had apparently turned to prone for the first time. In the 34 cases changed to prone, the change occurred <1 week before death for 21 infants; for 16 of those infants, death occurred the first or second time that they slept prone. In 56% of the cases changed from a nonprone to prone sleeping position, a caretaker other than the parents had precipitated the change. CONCLUSIONS: Ongoing campaigns to decrease the risk of SIDS should emphasize the risk of unaccustomed prone sleeping to both parents and secondary caretakers.

Female↗
PubMed1999

CUOG randomized trial of neoadjuvant androgen ablation before radical prostatectomy: 36-month post-treatment PSA results. Canadian Urologic Oncology Group.

OBJECTIVES: To test the hypothesis that neoadjuvant androgen ablation before radical prostatectomy reduces the likelihood of biochemical progression at 36 months. METHODS: Two hundred thirteen patients with localized prostate cancer were randomized to radical prostatectomy alone (Sx, n = 101) or a 12-week course of 300 mg of cyproterone acetate daily followed by surgery (CPA, n = 112). Biochemical progression (two consecutive detectable prostate-specific antigen [PSA] values) was determined for the entire group and by baseline PSA, Gleason score, clinical stage, and pathologic stage. RESULTS: The probability of biochemical progression at 36 months was similar in both groups (CPA 40.2%, Sx 30.1%; P = 0.3233). CPA patients with baseline serum PSA between 25 and 50 ng/mL had a lower probability of biochemical progression (CPA 63.5%, Sx 84.6%; P = 0.0038). No difference in the probability of biochemical progression was seen between groups when analyzed by clinical stage or Gleason score. When analyzed by pathologic margin status, no difference was observed in the probability of biochemical progression in patients with organ-confined disease (P = 0.4484). There was a trend for a higher probability of progression in the neoadjuvant arm in patients with positive and negative surgical margins (P = 0.0105, P = 0.0459; alpha = 0.005 with Bonferroni adjustment). CONCLUSIONS: Neoadjuvant androgen ablation with CPA reduces the positive margin rate significantly but does not result in a difference in biochemical progression at 3 years. This may be due to a lack of sufficient follow-up, insufficient power of the trial to demonstrate a small benefit, or a true lack of benefit of neoadjuvant androgen ablation before radical prostatectomy.

Androgen Antagonists↗
PubMed1999

Treatment with interferon beta-1b improves quality of life in multiple sclerosis.

BACKGROUND: The Canadian Burden of Illness Study Group reported that the quality of life (QoL) of multiple sclerosis (MS) patients falls drastically, early in the disease. With disability progression, the physical functioning scales of the Short Form 36 (SF-36) showed further decreases in QoL. The objective of this study is to describe the QoL of MS patients treated with interferon beta-1b (IFNB-1b) and to compare it to the QoL observed in a group of patients who had not been treated with IFNB-1b. METHODS: Treated patients were prospectively recruited and were seen at their regular visit to the MS clinic. They self-completed the SF-36 questionnaire and their QoL was described and retrospectively compared to that of historical controls. RESULTS: When IFNB-1b treated patients were compared to historical control patients with the same relapsing forms of MS, the treated patients with an Expanded Disability Status Scale (EDSS) score lower than 3.0 had a significantly better QoL. This was significant for four of the eight SF-36 domains: Physical Function (+22%, p = 0.0102), Role-Physical (+100%, p = 0.0022), General Health (+27%, p = 0.0070) and Social Function (+19%, p = 0.0287). The average QoL difference was 8% in the EDSS 3.0-6.0 group and 10% in the EDSS > 6 group. CONCLUSION: Patients with relapsing forms of MS treated with IFNB-1b have better QoL than patients who are not treated, especially those with an EDSS < 3.0.

Adolescent↗
PubMed1998

Peptide-based inhibitors of the hepatitis C virus serine protease.

Hexapeptide DDIVPC-OH is a competitive inhibitor of the hepatitis C virus (HCV) NS3 protease complexed with NS4A cofactor peptide. This hexapeptide corresponds to the N-terminal cleavage product of an HCV dodecapeptide substrate derived from the NS5A/5B cleavage site. Structure-activity studies on Ac-DDIVPC-OH revealed that side chains of the P4, P3 and P1 residues contribute the most to binding and that the introduction of a D-amino acid at the P5 position improves potency considerably. Furthermore, there is a strong preference for cysteine at the P1 position and conservative replacements, such as serine, are not well tolerated.

Amino Acid Sequence↗
PubMed1997

Synthesis and in vitro study of 17 beta-[N-ureylene-N,N'-disubstituted]-4-methyl-4-aza-5 alpha-androstan-3-ones as selective inhibitors of type I 5 alpha-reductase.

A series of 17 beta-(N-ureylene-N,N'-disubstituted)-4-azasteroids as inhibitors of human type I 5 alpha-reductase (5 alpha-Re) were prepared from 17 beta-N-alkyl-4-methyl-4-aza-5 alpha-androstan-3-ones and various isocyanates. For the measurement of 5 alpha-Re activity, 293 cells transfected with human type I 5 alpha-Re, cDNA were used. Azasteroids with an N-cyclopropyl ring exhibited potent inhibitory activity against type I 5 alpha-Re. As the chain length increased, from the N'-ethyl to the N'-butyl chain, activity of compounds also increased and azasteroids with the N'-butyl chain showed strong inhibitory activity (IC50 = 5.3 nM). Branching of alkyl chains decreased the potency of compounds. Introduction of the 1,2-double bond significantly reduced the activity of azasteroids. Replacement of the N'-alkyl chain with the phenyl moiety gave the most active compound of this series (IC50 = 1.3 nM). Other variations such as the replacement of a N-cyclopropyl ring with the N-methyl or the N-butyl chain decreased the activity of compounds (compounds were less active compared with above). The IC50 values of N-methyl-N'-cyclohexyl- and N-butyl-N'-phenyl-ureylenes were 31.5 and 11.5 nM. respectively. In general, all azasteroids were poor inhibitors of Type II 5 alpha-Re.

5-alpha Reductase Inhibitors↗
PubMed1996

Vinyl fluoride as a mimic of the "intermediate' enol form in the 5 alpha-reductase transformation: synthesis and in vitro activity of (N-1',1'-dimethylethyl)-3-haloandrost-3,5-diene-17 beta-carboxamides.

(N-1',1'-Dimethylethyl)-3-haloandrost-3,5-diene-17 beta-carboxamides (9-11) and the methyl ester 8 were prepared from 3-chloro/bromoandrost-3,5-diene-17 beta-carboxylic chloride/bromide (6/7), which were obtained from pregnenolone. In comparison with finasteride and 4-MA, compounds 8-11 showed very weak inhibitory activity ( < or = 10% inhibition) on human type I 5 alpha-reductase (transfected 293 cells) at 100 and 1000 nM concentrations. Against the type II enzyme, chloro compounds 8 and 9, and bromo 10 had no effect at 100 nM concentration, however, they were weak inhibitors of the type II (6.0% < inhibition < 30%) at a higher concentration. The best activity (IC50 = 480 nM) was observed with the 3-vinyl fluoride analogue 11.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1996

Randomized, prospective, controlled study comparing radical prostatectomy alone and neoadjuvant androgen withdrawal in the treatment of localized prostate cancer. Canadian Urologic Oncology Group.

PURPOSE: A prospective, multicenter, randomized study was done to test the hypothesis that neoadjuvant androgen withdrawal decreases the incidence of positive margins following radical prostatectomy for localized prostate cancer. MATERIALS AND METHODS: Observations were made of 213 patients randomized to undergo radical prostatectomy alone (101) or to receive a 12-week course of 300 mg. cyproterone acetate daily followed by surgery (112). Groups were similar at baseline in terms of clinical stage, serum prostate specific antigen and Gleason score. Of 192 patients available for efficacy analysis 9 had stage T1b, 8 stage T1c, 63 stage T2a, 36 stage T2b and 76 stage T2c disease. RESULTS: One or more positive surgical margins were found in 59 of 91 patients (64.8%) in the surgery only group compared to 28 of 101 (27.7%) in the cyproterone acetate group (p = 0.001). Patients who received preoperative therapy had a statistically significantly lower rate of apical margin involvement than those who did not (17.8 versus 47.8%, respectively, p < 0.0001). There was no statistically significant difference in surgical (p = 0.8645) or postoperative (p = 0.173) complications between the 2 groups. CONCLUSIONS: Neoadjuvant androgen withdrawal with a 12-week course of 300 mg. cyproterone acetate daily results in a lower rate of positive margins without adversely affecting postoperative recovery. The impact on patient survival will be determined by long-term followup.

Aged↗
PubMed1995

Synthesis and in vitro evaluation of 4-substituted N-(1,1-dimethylethyl)-3-oxo-4-androstene-17 beta-carboxamides as 5 alpha-reductase inhibitors and antiandrogens.

4-Substituted N-(1,1-dimethylethyl)-3-oxo-4-androstene-17 beta-carboxamides with the hydroxy (OH) 3d, mercapto (SH) 3e, chloro (Cl) 3f, and bromo (Br) 3g substituents at the 4-position were prepared in a two-step sequence with overall yields of 21%, 27%, 41%, and 37%, respectively. Compounds 3d-g showed weak inhibitory activity on human type I 5 alpha-reductase (IC50 > or = 700 nM) while they had intermediate inhibitory activity on human type II 5 alpha-reductase at IC50S of 172, 437, 192, and 387 nM, respectively. In androgen-sensitive Shionogi cells, the inhibition of dihydrotestosterone (DHT) stimulatory action on the proliferation of the androgen-sensitive cancer cells by all four compounds was high at IC50S of 170-279 nM compared with 117 nM for hydroxyflutamide. The present data show compounds having both moderate inhibition of human type II 5 alpha-reductase activity and relatively potent antiandrogenic action, two beneficial characteristics in the therapy of androgenic-sensitive diseases.

5-alpha Reductase Inhibitors↗
PubMed1993

Renal vein thrombosis in children: evidence of early flow recovery with Doppler US.

PURPOSE: To characterize renal arterial and venous Doppler signals in pediatric renal vein thrombosis (RVT) and to study changes in the circulation in the months following the acute event. MATERIALS AND METHODS: Ten patients with proved acute RVT (eight infants and two boys with renal allografts) were studied with serial Doppler ultrasonography (US) of the inferior vena cava and the main renal and intrarenal veins and arteries. RESULTS: The resistance index in the affected vessel was increased by 10% compared with that of the normal side in patients with unilateral RVT. Only the allografts had reversed diastolic flow. Venous flow, which was detected around the thrombus and in intrarenal veins in all native kidneys, was absent during the 1st week in the transplanted kidneys but reappeared thereafter in one. Perirenal collateral vessels were demonstrated with color Doppler US in one baby. Seven of eight native kidneys atrophied, and the allografts failed. CONCLUSION: Classic Doppler signs of RVT--absent venous flow and reversed diastolic arterial flow within the kidney--were present in only the acute phase in transplanted kidneys. These signs are unreliable in RVT of native kidneys.

Child↗
PubMed1990

Insight into protein nuclear magnetic resonance research.

Nuclear magnetic resonance (NMR) is one of the most powerful techniques to investigate the geometry of molecules in solution. It has been widely applied, in recent years, to the study of protein conformation. However, full reconstruction of the 3-D structure of such macro-molecules, still constitutes a real challenge for the spectroscopist. Skills as diverse as biology, spectroscopy, signal processing, or computer sciences, are required. This paper presents various aspects of the research in that domain, and our contribution to it.

Algal Proteins↗
PubMed1987

Actinomycin D facilitates transition of AT domains in molecules of sequence (AT)nAGCT(AT)n to a DNAse I detectable alternating structure.

The interaction of actinomycin D with (AT)nAGCT(AT)n (where n = 2, 3, or 4) was investigated using a combination of imino proton NMR and DNAse I digestion. The stoichiometry of the interaction appears to be one:one with the actinomycin chromophore intercalated between the two GC base pairs. This binding event facilitates the conversion of the flanking repetitive AT regions to an alternating conformation characterized by induced sensitivity of the ApT sequences to attack by DNAse I. The neighboring TpA sequences do not exhibit rate changes as a function of binding of the drug. The potential relevance of such ligand induced DNA structural alterations is discussed.

Adenine↗
PubMed1985

Single intralaminar thalamic neurons project to cerebral cortex, striatum and nucleus reticularis thalami. A retrograde anatomical tracing study in the rat.

The hypothesis of triple axonal branching to the cortex, striatum and nucleus reticularis thalami (RT) of the forebrain projecting thalamic intralaminar neurons (TIN) was studied by retrograde axonal transport of horseradish peroxidase (HRP), iron-dextran complex and [3H]wheat germ agglutinin [3H]WGA. The best combination of tracers for this purpose was demonstrated to be: HRP-pellet implantation in the rostral cortex, iron-dextran injections into the striatum and [3H]WGA injections into the rostral RT. Prussian blue labeled neurons were observed in the ipsilateral TIN, substantia nigra, mediodorsal nucleus, medial part of the ventral anterior-ventral lateral complex, anterior medial and anterior ventral nuclei. HRP labeled neurons were observed in ipsilateral ventral nuclei, mediodorsal nucleus and the TIN. Radiolabeled neurons were located only in the TIN. HRP-Prussian blue labeled neurons (cortex-striatum branched neurons) were scattered in the TIN. Prussian blue radiolabeled neurons (striatum-RT branched neurons) could be observed in the TIN, as well as a few HRP radiolabeled neurons (cortex-RT branched neurons). Triply labeled neurons were scattered throughout the TIN until the rostral part of the centre median nucleus. These results demonstrate the existence of triple axonal branching on TIN efferent axons directed to the cerebral cortex, striatum and RT. The RT directed branch provides an anatomical basis to describe an intrathalamic regulatory loop well suited to control ascending messages arising from the TIN.

Animals↗
PubMed1984

Inferior olivary neurons: 3-acetylpyridine effects on glucose consumption, axonal transport, electrical activity and harmaline-induced tremor.

The effects of 3-acetylpyridine (3-AP) on the neurons in the inferior olive (IO) were studied by several methods to establish the time-order of events due to the neurotoxicity of 3-AP in the rat. It was found that IO metabolism, studied with [14C]2-deoxyglucose, began to decrease detectably 1 h after 3-AP and was totally suppressed at 3 h. Retrograde axonal transport of lectin horseradish peroxidase (HRP) from cerebellar cortex to the IO was also totally suppressed 3 h after 3-AP and in fact showed a time course similar to that for the suppression of metabolism. Harmaline produced tremor has been shown to induce rhythmic activity and increase glucose consumption in the IO. When injected in 3-AP treated animals, harmaline produced its usual effects at 2 h after the 3-AP but had no effects after 3 h. The present results indicate that the neurotoxic effects of 3-AP are not simply graded in time, but tend to have the greatest effects between the 2nd and 3rd hour following its administration.

Alkaloids↗
PubMed1984

Harmaline induced tremor. III. A combined simple units, horseradish peroxidase, and 2-deoxyglucose study of the olivocerebellar system in the rat.

Purkinje cells were recorded extracellularly and mapped in the cerebellar cortex of the rat under tremogenic doses of harmaline. Four different types of responses were encountered, of which two were considered as being responsible for the harmaline tremor. The latter had a regular firing pattern of complex spikes at 5 to 10 Hz and were mostly found in the vermis. Their number decreased in the more lateral region of the cerebellar cortex until they eventually disappeared. Horseradish peroxidase was injected into all the areas of the cerebellar cortex containing Purkinje cells with harmaline-induced activity. Labeled neurons were in all cases traced to the medial accessory olive. The metabolic activity of the inferior olive under harmaline was measured with 2-deoxyglucose. Increased labeling was only found in the medial accessory olive. Such an increase was demonstrated as being due to a direct effect of the drug on the inferior olivary neurons, indicating that the medial accessory olive is responsible for the harmaline tremor in the rat. Our results point out that, in the rat, there is an inverse relationship between serotoninergic innervation of a region in the inferior olivary nucleus and that with harmaline sensitivity, therefore a serotoninergic mechanism hypothesis for the harmaline tremor needs further investigation.

Alkaloids↗
PubMed1983

Simultaneous visualization of Nuclear yellow and iron-dextran complex for demonstration of branched neurons by retrograde axonal transport.

Retrogradely transported iron-dextran complex and Nuclear yellow could be demonstrated simultaneously on the same sections of rat CNS. Using combined bright-field and ultraviolet illuminations, double labeled neurons were observed. They exhibited a fluorescent nucleus and cytoplasmic Prussian blue granules. Thus, the combination of these two tracers appeared to be a convenient method for the anatomical demonstration of collaterals.

Animals↗