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Biomedical subjects

M Roy

Publications and source records attributed to M Roy.

At least 37 records · Page 2Linked to original sources
PubMed2001

Family history and the risk of coronary heart disease: comparing predictive models.

Family history is commonly used when evaluating coronary heart disease (CHD) risk yet it is usually treated as a simple binary variable according to the occurrence or non-occurrence of disease. This definition however fails to consider the potential components of a family history which may in fact exert different degrees of influence on the overall risk profile. The purpose of this paper is to compare different predictive models for CHD which incorporate family history as either a binary variable or different types of family risk indices in terms of their predictive ability. Models for estimating CHD risk were constructed based on usual risk factors and different family history variables. This construction was accomplished using logistic regression and RECursive Partition and AMalgamation (RECPAM) trees. Our analyses demonstrate the importance of using more sophisticated definitions of family history variables compared to a simple binary approach since this leads to a significant improvement in the predictive ability of CHD risk models.

Adult↗
PubMed2001

Effect of interleukin-2 and selenium on the growth of squamous cell carcinoma cells.

OBJECTIVES: The objectives of this study were to determine whether the expression of the interleukin-2 (IL-2) receptors on squamous cell carcinoma cells can be enhanced in the presence of selenium (Se) and contribute to a greater retardation of tumor growth after locoregional therapy with IL-2. STUDY DESIGN: The growth of the cells was studied after in vitro or dietary supplementation with Se in a murine model. RESULTS: Treatment of established tumors in hosts supplemented with Se with peritumoral injections of IL-2 resulted in 50% reduction of tumor size, whereas treatment of early tumors resulted in 72.4% reduction. The effect was most likely related to a combination of enhanced immune responsiveness and enhanced IL-2 receptor expression on the tumor cells. CONCLUSIONS AND SIGNIFICANCE: The data suggested that local immunotherapy with IL-2 in hosts supplemented with Se may represent an effective modality of treatment for the prevention of recurrences at the site of conventionally treated primary tumors, including tumors that do not express IL-2 receptors.

Animals↗
PubMed2001

Electroretinogram and cue-elicited craving in withdrawn cocaine-dependent patients: a replication.

BACKGROUND: We previously reported that cocaine-dependent patients with a reduced blue cone b wave electroretinogram (ERG) responses had significantly more cue-elicited craving. METHODS: A new series of 21 recently withdrawn cocaine-dependent patients completed a craving questionnaire at baseline and following cue exposure; an ERG was also performed. RESULTS: Cocaine-dependent patients with a blunted ERG blue cone response (<0.5 microV) showed greater increases in craving following cue exposure. When subjects were included from our preliminary study (N = 14), these differences became highly significant. CONCLUSIONS: Patients with a reduced ERG response may represent a subgroup more vulnerable to cocaine craving and future relapse.

Adolescent↗
PubMed2001

New approaches in the surgical management of early stage cervical cancer.

Quality of life has become a very important issue in deciding the extent of surgical procedures for patients affected with a variety of cancers. In recent years, more attention has been given to preserving organ function, cosmesis, and now reproductive function. As cancer treatment has improved survival in several neoplasias, cancer survivors are becoming more interested in preserving their fertility potential. We focus here on new surgical advances in the management of early stage cervical cancer, with emphasis on the radical trachelectomy technique to preserve fertility potential and the Saling procedure to prevent premature labor. We also discuss the issue of the sentinel node localization.

Female↗
PubMed2001

Ethnic differences in distributions of GSTM1 and GSTT1 homozygous "null" genotypes in India.

We estimated the frequencies of GSTM1 and GSTT1 "null" homozygotes in 10 different ethnic populations of India by a genotyping method based on polymerase chain reaction. These populations, inhabiting diverse geographical locations and occupying various positions in the sociocultural hierarchy, were represented by a sample of 299 unrelated individuals. Frequencies of GSTM1 and GSTT1 "null" homozygotes varied from 20% to 79% and 3% to 39%, respectively, across the study populations. Maximum frequencies of GSTM1 and GSTT1 "null" homozygotes (79% and 39%, respectively) have been observed in the same population (Jamatia). Frequencies of homozygous "null" genotypes at the GSTM1 and GSTT1 loci show a significant positive correlation in these populations, which is contrary to expectations. A possible implication is that the two enzymes are working in tandem, instead of working in a complementary way.

Cluster Analysis↗
PubMed2001

Managing atypical squamous cells of undetermined significance in Papanicolaou smears.

OBJECTIVE: To assess strategies using repeated conventional Pap smear and human papillomavirus (HPV) DNA testing, alone or in combination, for identifying women with concomitant cervical intraepithelial neoplasia 2 and 3 (CIN 2/3) in women with atypical squamous cells of undetermined significance (ASCUS) in their Pap smears. STUDY DESIGN: A total of 360 women cytologically diagnosed with ASCUS were referred for colposcopy and underwent a repeat Pap smear, a biopsy when necessary and HPV testing using three different modes of detection of high-oncogenic-risk HPV types: 1, first-generation Hybrid Capture test (HC-1) (Digene Diagnostics, Gaithersburg, Maryland); 2, second-generation Hybrid Capture test (HC-2); and 3, polymerase chain reaction (PCR). RESULTS: Nineteen patients (5.3%) had histologic CIN 2/3. The sensitivity and specificity of the repeat Pap smear alone for the detection of CIN 2/3 were 73.7% and 62.9%, respectively, when referring all women with a repeat Pap smear using an ASCUS-positive threshold. The proportion of women referred for colposcopy was 39.0%. When HPV testing for high risk was used for identification of women with histologic CIN 2/3, sensitivity and specificity were, respectively, 68.4% and 85.9% for HC-1, 89.5% and 73.9% for HC-2 and 89.5% and 59.0% for PCR. The rate of referral for colposcopy of these three modes of HPV testing was 16.9%, 29.4% and 44.0%, respectively. The sensitivity and specificity for identification of women with concomitant CIN 2/3 using a combination of repeat cytology showing a low grade squamous intraepithelial lesion or high grade squamous intraepithelial lesion and/or a test positive for high-oncogenic-risk HPV group were, respectively, 94.7% and 73.2% when used in combination with HC-2. The referral rate of women for colposcopy of this combined strategy was 30.4%. CONCLUSION: As compared to the strategy using abnormal repeat Pap smear alone, those using high-risk HPV testing with Hybrid Capture showed statistically significantly higher specificities and lower proportions of women with ASCUS referred for colposcopy. In particular, a promising strategy would be to refer for colposcopy only women with repeat Pap smears showing squamous intraepithelial lesion and/or those positive for high-risk HPV detected by Hybrid Capture testing.

Adolescent↗
PubMed2000

Isoform-specific differences between the type Ialpha and IIalpha cyclic AMP-dependent protein kinase anchoring domains revealed by solution NMR.

Cyclic AMP dependent protein kinase (PKA) is controlled, in part, by the subcellular localization of the enzyme (). Discovery of dual specificity anchoring proteins (d-AKAPs) indicates that not only is the type II, but also the type I, enzyme localized (). It appears that the type I enzyme is localized in a novel, dynamic fashion as opposed to the apparent static localization of the type II enzyme. Recently, the structure of the dimerization/docking (D/D) domain from the type II enzyme was solved (). This work revealed an X-type four-helix bundle motif with a hydrophobic patch that modulates AKAP interactions. To understand the dynamic versus static localization of PKA, multidimensional NMR techniques were used to investigate the structural features of the type I D/D domain. Our results indicate a conserved helix-turn-helix motif in the type I and type II D/D domains. However, important differences between the two domains are evident in the extreme NH(2) terminus: this region is extended in the type II domain, whereas it is helical in the type I protein. The NH(2)-terminal residues in RIIalpha contain determinants for anchoring, and the orientation and packing of this helical element in the RIalpha structure may have profound consequences in the recognition surface presented to the AKAPs.

Amino Acid Sequence↗
PubMed2000

Effects of aerobic physical exercise in the elderly with type 2 diabetes mellitus.

The objective of this study was to determine the impact of an aerobic physical exercise program in the treatment of a group of elderly patients with type 2 diabetes mellitus (DM) in relation to metabolic control, physical capacity, quality of life (QOL) and attitudes toward diabetes. Patients were randomly assigned to either an experimental (n=19) or a control (n=20) group. The following measurements were conducted at baseline and after week 16: glycosylated hemoglobin (hbA1c), fructosamine, 3 h oral glucose tolerance test, treadmill test (Balke-Naughton), and a questionnaire on QOL and attitudes toward DM. After the intervention, the experimental group showed a significant decrease of glucose excursion during the oral glucose tolerance test (OGTT) (area under the curve) (16.6+/-3.8 vs. 15.3+/-3.1, P<0.05) and an increase in total time on the treadmill (s) (423+/-207 vs. 471+/-230, P<0.05). An improvement in the attitudes toward DM was observed in the experimental group (P=0.01) but not in the control group. Female gender, higher body mass index and hbA1c were factors associated with a response to the intervention. This study suggests that physical exercise has significant effects on glucose excursion during an OGTT and exercise tolerance in elderly patients with type 2 DM.

Journal Article↗
PubMed2000

Occurrence of sulfate-reducing bacteria under a wide range of physico-chemical conditions in Au and Cu-Zn mine tailings.

Sulfate-reducing bacteria (SRB) have been observed in mining environments, but their presence has not been linked to specific physico-chemical and mineralogical factors. The present study was undertaken to assess the presence of SRB in several Au and Cu-Zn mine tailings located near Timmins, Ont., Canada, and determine the factors responsible for their presence. Vegetated and non-vegetated mine tailings were sampled for SRB enumeration, pH, Eh, water content, total carbon content and sequential chemical extraction. Results first showed that SRB populations were present at all sites and that their distribution varied with depth. Populations were recovered from neutral pH and slightly anoxic tailings and from highly acidic (pH 2) and oxic tailings. The total carbon content of the tailings was generally low and not related to the presence of vegetation. In addition, the carbon content did not affect SRB population distribution and appeared to be more related to the type of tailings, i.e., oxidized and acidic Cu-Zn tailings contained on average more carbon than Au tailings. Results also indicated that the water content of the tailings varied greatly with depth and was not related to the presence of SRB populations. The sequential chemical extraction showed that the pyrite content of the tailings was lower in Au tailings than in Cu-Zn tailings, and that some oxidized Cu-Zn sites were depleted in pyrite due to microbial and chemical oxidation. Our results indicate that SRB could be cultured from a variety of sites and sample types, and that factors such as pH, Eh, water content and carbon content at the collection sites did not exert control on their presence.

Journal Article↗
PubMed2000

An essential intermediate in the folding of dihydrofolate reductase.

The folding of Escherichia coli dihydrofolate reductase was examined at pH 7.8 and 15 degrees C by using stopped-flow fluorescence and absorbance spectroscopies. The formation of a highly fluorescent intermediate occurs with relaxation times ranging between 142 and 343 msec, whereas stopped-flow absorbance spectroscopy using methotrexate binding assays shows a distinct lag phase during these time frames for the native state. The lag in absorbance kinetics and the lack of fast-track folding events indicate that the formation of this ensemble of intermediates is an obligatory step in the folding reaction.

Bacterial Proteins↗
PubMed2000

Aggregation events occur prior to stable intermediate formation during refolding of interleukin 1beta.

A point mutation, lysine 97 --> isoleucine (K97I), in a surface loop in the beta-sheet protein interleukin 1beta (IL-1beta), exhibits increased levels of inclusion body (IB) formation relative to the wild-type protein (WT) when expressed in Escherichia coli. Despite the common observation that less stable proteins are often found in IBs, K97I is more stable than WT. We examined the folding pathway of the mutant and wild-type proteins at pH 6.5 and 25 degrees C with manual-mixing and stopped-flow optical spectroscopy to determine whether changes in the properties of transiently populated species in vitro correlate with the observation of increased aggregation in vivo. The refolding reactions of the WT and K97I proteins are both described by three exponential processes. Two exponential processes characterize fast events (0.1-1.0 s) in folding while the third exponential process correlates with a slow (70 s) single pathway to and from the native state. The K97I replacement affects the earlier steps in the refolding pathway. Aggregation, absent in the WT refolding reaction, occurs in K97I above a critical protein concentration of 18 microM. This observation is consistent with an initial nucleation step mediating protein aggregation. Stopped-flow kinetic studies of the K97I aggregation process demonstrate that K97I aggregates most rapidly during the earliest refolding times, when unfolded protein conformers remain highly populated and the concentration of folding intermediates is low. Folding and aggregation studies together support a model in which the formation of stable folding intermediates afford protection against further K97I aggregation.

Amino Acid Substitution↗
PubMed2000

Combined laparoscopic and vaginal radical surgery in cervical cancer.

OBJECTIVE: The purpose of our study was to review our experience with laparoscopic staging and vaginal radical surgery in the treatment of early stage cervical cancer. STUDY DESIGN: We reviewed the charts of 102 patients who had a laparoscopic pelvic lymphadenectomy followed by vaginal radical hysterectomy (VRH) or vaginal radical trachelectomy (VRT). RESULTS: Patients' age ranged from 25 to 68 years (median: 36). Squamous and adenocarcinoma histology occurred in 68 and 32%, respectively. Stage Ib1 occurred in 77% of cases and the rest were stage Ia1 (1%), 1a2 (16%), and IIa (6%). Patients were divided into three groups: VRH (57), VRT (34), and node only (NO) (11), when positive nodes were identified on frozen section. Median operative time for VRH and VRT were 270 and 260 min compared to 200 min in the NO group (half also had bilateral paraaortic node dissection, which lengthened the OR time). Hospital stay was shorter in the NO group (2 days). For each group (VRH, VRT, and NO) the median pelvic node count was 27, 26, and 23 and the median paraaortic node count was 3, 4, and 9. Two VRH were converted to an abdominal procedure because of technical difficulties and one VRT was converted to a VRH because of positive endocervical margins. Intraoperative complications related to laparoscopy included two iliac and one epigastric vessel injuries. Complications related to the radical surgeries included three cystostomies, managed vaginally, and a laparotomy for parametrial bleeding after VRT. Postoperative complications occurred in 6% of patients and only one was considered major (an abscess which required surgical drainage). Overall, there were only four recurrences in the vaginal surgery groups and one in the NO group. There were no ureteral or intestinal injuries and there have been no trocar site recurrences. CONCLUSION: Our data show that approaching cervical cancer with a combined laparoscopic and vaginal surgery is feasible. The overall morbidity and complication rate are low and the lymph node count is satisfactory. Staging the nodes laparoscopically first to identify positive nodes is advantageous, particularly since we favor the use of chemoradiation therapy in those cases. The laparoscopic node staging thus avoids an unnecessary laparotomy in patients with positive nodes, reduces morbidity, and allows for early radiation therapy.

Adenocarcinoma↗
PubMed2000

Evaluating contraceptive choice through the method-mix approach. An Indian Council of Medical Research (ICMR) task force study.

The method-mix approach was used to evaluate informed contraceptive choices in the present study. A total of 8,077 potential clients were given a balanced presentation of all available contraceptive methods in the national program, ie, the CuT 200 intrauterine device (IUD), low-dose combined oral pills (OC), condom, and sterilization (female/male) along with a new method, Norplant(R).(1) The majority of women opted for spacing methods; among them, the IUD was preferred by about 60% of clients, followed by condoms (9%), OC (6%), and Norplant (5%). Sterilization, mainly female, was accepted by about 17% of the women making an informed choice. The economic status of couples did not influence the contraceptive choices, as all the methods were offered free of cost in the present study, which is the current practice in the national program. Illiterate women more often accepted sterilization (about 25%) than did literate women (15%). This is because illiterate women had more children; about 30% of illiterate women had three or more children, as opposed to 16.2% of literate women. However, literacy status did not influence the choice of any specific spacing method. The study also revealed that, by encouraging potential clients to make an informed choice, they could override the provider's bias while accepting a particular type of spacing method. This is evident from the observation that Norplant was the first choice of the provider for 35% of the women, whereas only 5% of women preferred and accepted Norplant. The present study stresses an urgent need to promote the practice of informed choices in the national program with a variety of contraceptive options-especially, spacing methods for improving contraceptive prevalence and reproductive health in the country.

Adolescent↗
PubMed2000

Coexisting dysbetalipoproteinemia and familial hypercholesterolemia. Clinical and laboratory observations.

Type III dysbetalipoproteinemia and familial hypercholesterolemia (FH) are two metabolic disorders giving rise to severe disturbances of lipid homeostasis and premature atherosclerosis. Both metabolic abnormalities have a genetic basis and co-occurrence in the same patient has seldom been described. Because of the unique structure of the French Canadian population, there was an opportunity to observe patients with both dysbetalipoproteinemia (E2/2 homozygotes) and FH (N=14) and to compare their clinical data with that of patients with type III (N=75), patients with FH (N0.7 and the presence of beta-VLDL on electrophoresis. Presence of a low density lipoprotein receptor, LDL-R, mutation should be suspected in a type III patient with a LDL-C level above 3.0 mmol/l and a family history of premature CAD. In the group of patients studied, the coexistence of dysbetalipoproteinemia and heterozygous FH does not appear to increase the prevalence of cardiovascular complications above that observed among control type III or control E3/3-FH patients. Thus, the presence of two epsilon2 alleles in these patients affects the expression of the abnormal LDL-R allele and the resulting phenotype substantiates the non additive effects of alleles at these two loci (epistasis).

Adult↗