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Biomedical subjects

M Roy

Publications and source records attributed to M Roy.

At least 145 records · Page 8Linked to original sources
PubMed1995

The use of operative laparoscopy in determining eligibility for pelvic exenteration in patients with recurrent cervical cancer.

In patients with suspected recurrent cervical cancer after radiation therapy, it can be very difficult to pathologically confirm recurrence and clinically determine if tumor is resectable via a curative pelvic exenteration. Despite very thorough preoperative investigation uncertainties often remain, so patients ultimately undergo exploratory laparotomy. Unfortunately, inoperable disease is frequently discovered then. We report the use of operative laparoscopy in three patients with recurrent stage IIIB cervical cancer. The age ranged from 38 to 79 years. The mean duration of the procedure was 146 min (range 110-180 min) and blood loss was minimal. The procedure was well tolerated in all patients. There was no intraoperative complication but one deep thrombophlebitis occurred postoperatively. The procedure was successful in all cases in confirming recurrence and selecting out patients who were not surgical candidates for pelvic exenterations. Operative laparoscopy is a less invasive procedure that may be a valuable step in the workup of patients with recurrent cervical cancer. With experience in retroperitoneal surgery, the procedure can be carried out safely. We believe that this approach could prevent unnecessary laparotomies, shorten the hospital stay and the postoperative recovery, and contribute to a better quality of life for women with inoperable disease.

Adult↗
PubMed1995

Evidence for a cholesterol-lowering gene in a French-Canadian kindred with familial hypercholesterolemia.

We describe a four-generation kindred with familial hypercholesterolemia (FH) in which two of the eight heterozygotes for a 5-kb deletion (exons 2 and 3) in the low density lipoprotein (LDL) receptor gene were found to have normal LDL-cholesterol levels. In our search for a gene responsible for the cholesterol-lowering effect in this family, we have studied variation in the genes encoding the LDL receptor, apolipoprotein (apo) B, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, apoAI-CIII-AIV, and lipoprotein lipase. The analysis showed that it was unlikely that variation in any of these genes was responsible for the cholesterol-lowering effect. Expression of the LDL receptor, as assessed in vitro with measurements of activity and mRNA levels, was similar in normo and hyperlipidemic subjects carrying the deletion. Analysis of the apo E isoforms revealed that most of the e2 allele carriers in this family, including the two normolipidemic 5-kb deletion carriers, were found to have LDL-cholesterol levels substantially lower than subjects with the other apo E isoforms. Thus, this kindred provides evidence for the existence of a gene or genes, including the apo e2 allele, with profound effects on LDL-cholesterol levels.

Cholesterol↗
PubMed1995

New methods for rapid detection of low-density lipoprotein receptor and apolipoprotein B gene mutations causing familial hypercholesterolemia.

Due to a genetic founder effect, five mutations in the low-density lipoprotein receptor gene account for approximately 83% of familial hypercholesterolemia (FH) diagnosed in French-Canadians. The most frequent mutation, present in 61% of heterozygotes, is a > 10 kb deletion of the 5' region of the gene that removes the promoter and the first exon, resulting in a null allele. Other less prevalent mutations include a gene deletion of approximately 5 kb, which removes exons 2 and 3 (2% of cases) and three missense mutations: Trp66-->Gly (exon 3) (12%), Glu207-->Lys (exon 4) (3%), and Cys646-->Tyr (exon 14) (6%). The apoB Arg3500-->Gln mutation was absent in 228 French Canadians with the FH phenotype. Taking advantage of the availability of fluorescent DNA detection, we have substantially improved the assays for these mutations.

Adult↗
PubMed1995

Neonatal thrombosis: are we doing the right studies?

Although neonatal thrombosis may be fatal or cause serious morbidity in survivors, strong clinical recommendations on the management of affected infants could not be made in the 1980s because of the lack of sound data from high-quality studies. To determine whether the "right" studies are now being done, a Medline search (exp infant, newborn, and exp thrombosis) for English language articles 1991-1994, was done and 135 citations were found. After exclusion of 59 nonrelevant articles (such as thrombosis in pregnant women or in vitro studies), plus nine letters to the editor, two reviews, and one consensus report, 64 original articles remained. Eighty-four percent of those (54 citations) were case reports and small case series. Experimental designs (prospective or retrospective cohort and case-control studies) were used in only 10 reports. The recently published literature on neonatal thrombosis continues to show an overabundance of anecdotal reports and a shortage of well-designed collaborative studies. The latter are sorely needed to improve the management of affected infants.

Female↗
PubMed1995

Impact of a common mutation of the LDL receptor gene, in French-Canadian patients with familial hypercholesterolemia, on means, variances and correlations among traits of lipid metabolism.

Structural and functional studies of the gene coding for the low density lipoprotein receptor in patients with familial hypercholesterolemia have uncovered over 180 mutant alleles of the gene. Although the classical familial hypercholesterolemia phenotype is well known, the range of phenotypic variability in lipid traits associated with particular mutations in familial hypercholesterolemia has not been extensively documented. We investigated the phenotypic distributions of plasma markers of lipid metabolism from a large sample of unrelated individuals who are heterozygous for a single mutation, a > 10 kb deletion in the low density lipoprotein receptor gene, and compared these distributions with those from a sample of healthy controls. Patients were pair-matched for sex and age with healthy individuals selected from a previously studied French-Canadian population from the same region. We examined the level and variation of seven lipid traits, the correlations between the traits, and the amount of overlap of the sample distributions for each trait. The low density lipoprotein receptor defect was found to affect the levels and variability of traits, and correlations between traits. There was some overlap of the distributions of lipid traits including that for low density lipoprotein cholesterol, which is a cardinal feature of familial hypercholesterolemia. The low density lipoprotein receptor gene has a sex-specific pleiotropic effect and should be considered as a variability gene as well as a level gene. The extensive dynamic changes observed in the relationships between lipid traits testify to the biological complexity of genome type-environment interactions.

Adult↗
PubMed1995

Supplementation with selenium restores age-related decline in immune cell function.

This study examined the effect of dietary (2.00 ppm for 8 weeks) supplementation with selenium (as sodium selenite) on the ability of lymphocytes from aged (24-month-old), male, C57BL/6JNIA mice to respond to: (i) stimulation with mitogen (phytohemagglutinin) or alloantigen; (ii) develop into cytotoxic effector cells; and (iii) destroy tumor cells. Supplementation with selenium resulted in a significant increase in the ability of spleen lymphocytes from aged animals to undergo blastogenesis, as indicated by significantly higher amounts of nuclear incorporation of 3H-thymidine after stimulation with mitogen. The dietary regimen restored the age-related deficiency of the cells to respond to stimulation by nuclear DNA synthesis and cell proliferation, at least, to the level of cells from unsupplemented young adult animals. Furthermore, populations of in vivo, alloantigen-activated lymphocytes from Se-supplemented aged animals contained significantly higher numbers of cytotoxic lymphocytes than those from Se-normal aged animals, which resulted in an enhanced capacity to destroy tumor cells. The significant increase in the number of cytotoxic effector cells within these activated T-lymphocyte populations was probably the result of an enhanced clonal proliferation of cytotoxic precursors cells, followed by the differentiation of greater numbers of cytotoxic effector cells. This effect occurred in the absence of changes in the ability of the cells to produce IL-2, which confirmed our earlier observation that dietary supplementation with selenium does not affect the production of IL-2. The data suggested that selenium restores the age-related defect in cell proliferation through an increase in the number of high-affinity IL-2 receptors.

Aging↗
PubMed1995

Prevalence of alleles encoding defective lipoprotein lipase in hypertriglyceridemic patients of French Canadian descent.

It has previously been estimated that due to genetic "founder effects," 97% of lipoprotein lipase (LPL) gene alleles conferring type I hyperlipoproteinemia (HLP) in French Canadians encode one of the following mutant LPL forms: Gly188-->Glu, Pro207-->Leu, or Asp250-->Asn. Although the genetic basis of type I HLP is known to be homozygosity for LPL deficiency, that for other forms of HLP, especially types IV, and V HLP, is not clear. It is also unclear whether hypertriglyceridemia due to very low density lipoprotein (VLDL) overproduction can be distinguished phenotypically from that due to defective catabolism of plasma lipoprotein triglycerides. The present study took advantage of the unique circumstances inherent in the relatively genetically isolated French Canadian population to address these questions. This study was carried out in order to determine the prevalence of these three mutant LPL alleles, and of a fourth encoding LPL Asn291-->Ser, in French Canadian patients with hypertriglyceridemia. The prevalence of heterozygosity for one of the four LPL mutant alleles in nondiabetic, nonobese hypertriglyceridemic subjects was 16 of 95 type IV HLP (17%) and 4 of 26 type V HLP cases (15%). These alleles were not found in over 150 normotriglyceridemic subjects, supporting the likelihood that the mutant alleles were at least partially responsible for HLP. In addition, heterozygosity for LPL deficiency due to one of these mutations apparently did not contribute to hypoalphalipoproteinemia, and was observed in 3 of 39 subjects with type III HLP. The results suggest that in French Canadians, 15-20% of type IV and V HLP cases are associated with these genetic defects in plasma triglyceride catabolism.

Adult↗
PubMed1995

Study of benign superficial cysts by fine needle aspiration cytology.

Fine needle aspiration cytology of 213 cases of different cystic lesions from various regions of body and different superficial organs was analysed in an attempt to present the experience of the authors in the diagnosis of such lesions. The predominant lesion diagnosed by fine needle aspiration cytology was adnexal cyst/sebaceous cyst (41 cases) followed by vascular hamartoma (40 cases) and thyroglossal cyst (9 cases). One hundred fifty-eight (74.2%) out 213 cases were confirmed histopathologically. There was false negative diagnosis in 14 cases (6.6%). The remaining 41 (19.2%) cases did not turn up for further treatment. The fallacies that have been recorded in the diagnosis of thyroid cysts, salivary gland cysts and breast cysts in respect of papillary cystic thyroid carcinoma, muco-epidermoid carcinoma of salivary gland and intraductal carcinoma with fibrocystic disease of breast respectively have been highlighted in the present study.

Biopsy, Needle↗
PubMed1995

Fine needle aspiration cytology of bone and joint lesions: an assessment.

Fine needle aspiration cytology and subsequent correlation with histology and therapeutic follow-up was done in 198 cases of bone and joint lesions. Overall accuracy was found to be 87.34%; false diagnosis was recorded in 4.5% of cases; 8.08% cases were excluded from correlation as they did not turn up for further treatment or follow-up after the diagnosis. False diagnosis was encountered mostly with inflammatory lesions and primary neoplasms, diagnosing osteosarcoma and Ewing's sarcoma as chronic inflammatory lesion, chondroma as chondrosarcoma and vice versa. The possible cause of default has been discussed. The benign cystic lesions could be diagnosed with almost 100% accuracy by fine needle aspiration cytology where 10% cases were excluded as they could not be followed up.

Biopsy, Needle↗
PubMed1995

Adaptive control of therapeutic drug regimens relations between clinical situations: outcomes and simulations using nonlinear dynamic models.

With Bayesian modeling and adaptive control of drug dosage regimens, serum and peripheral drug concentrations can be predicted in clinical situations using linear pharmacokinetic compartmental models (PK). Recently, several pathophysiologic and pharmacodynamic nonlinear models (PD) have been developed. The present report illustrates both their utility and limits for the computation of effects in clinical situations in the setting of actual routine and acute patient care. Patients who received therapy with aminoglycosides or/and vancomycin were selected. For each patient, after estimation of individual pharmacokinetic parameters, the computed outputs of the linear compartmental pharmacokinetic model were used as inputs for 2 different a priori nonlinear dynamic models: 1) the EFFECT modeling program, using a Hill model, and 2) the BACTCIDE program, which is a combination of a simple growth model for the organism and a Hill effect model considering both the microorganism, the antibiotic, and the patient's minimal inhibitory concentration (MIC). The programs (1) and (2) can use as inputs the computed concentrations from any of three compartments: central, peripheral, or a spherical diffusion compartment to compute drug diffusion into endocardial vegetations or abscesses. The EFFECT program can be used alone for the evaluation of drug effects. The BACTCIDE program illustrates differences in activity between concentration-dependent and time-dependent antibiotics. Such nonlinear programs are very sensitive to the MIC values.

Aged↗
PubMed1994

Risk factors for cervical intraepithelial neoplasia: differences between low- and high-grade lesions.

This case-control study assesses relations of human papillomavirus (HPV) type 16 infection, sexual history, cigarette smoking, and oral contraceptive use to low- and high-grade cervical intraepithelial neoplasia (CIN). A total of 548 high-grade and 338 low-grade CIN cases and 612 controls were identified among women seen at a colposcopy clinic in Quebec, Quebec, Canada, in 1988-1989. Interviews, colposcopy, cervical scrapings, and colposcopically directed biopsies were performed. One pathologist reviewed all histologic slides. Southern blot techniques were used to assay specimens for HPV 16 DNA. Lifetime number of sexual partners was related to low- and high-grade CIN. Presence of HPV 16 DNA was associated with a 8.7-fold (95% confidence interval 5.1-15.0) elevation in estimated relative risk of high-grade CIN. Relative risk of high-grade CIN increased with amount of HPV 16 DNA (p < 0.0001). Estimated relative risk of high-grade CIN in current cigarette smokers was 2.4 (95% confidence interval 1.8-3.2) compared with never smokers and increased with number of pack-years of exposure (p < 0.0001). Long-term (6 years or more) users of oral contraceptives had an estimated relative risk of high-grade CIN of 1.9 (95% confidence interval 1.1-3.3) compared with those who never used such contraceptives. In contrast, presence of HPV 16 DNA, cigarette smoking, and oral contraceptive use showed little or no relation to low-grade CIN. Risk factors for low- and high-grade CIN may differ substantially.

Adult↗
PubMed1994

High-resolution structure of an engineered biologically potent insulin monomer, B16 Tyr-->His, as determined by nuclear magnetic resonance spectroscopy.

Site-directed mutagenesis is used in conjunction with 1H nuclear magnetic resonance (NMR) and circular dichroism (CD) spectroscopy in order to find an insulin species amenable for structure determination in aqueous solution by NMR spectroscopy. A successful candidate in this respect, i.e., B16 Tyr-->His mutant insulin, is identified and selected for detailed characterization by two-dimensional 1H NMR. This mutant species retains 43% biological potency and native folding stability, but in contrast to human insulin it remains monomeric at millimolar concentration in aqueous solution at pH 2.4. The resulting homogeneous sample allows high-quality 2D NMR spectra to be recorded. The NMR studies result in an almost complete assignment of the 1H resonance signals as well as identification of NOE cross peaks. NOE-derived distance restraints in conjunction with torsion restraints based on measured coupling constants, 3JHNH alpha, are used for structure calculations using the hybrid method of distance geometry and simulated annealing. The calculated structures show that the major part of the insulin monomer is structurally well-defined with an average rms deviation between the 20 calculated structures and the mean coordinates of 0.89 A for all backbone atoms, 0.46 A for backbone atoms (A2-A19 and B4-B28), and 1.30 A for all heavy atoms. The structure of the A-chain is composed of two helices from A2 to A7 and from A12 to A19 connected by a short extended strand. The B-chain consists of a loop, B1-B8, an alpha-helix, B9-B19, a beta-turn, B20-B23, and an extended strand from B24 to B30.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1994

A randomized prospective study comparing three techniques of conization: cold knife, laser, and LEEP.

Three different techniques of cervical excision, cold knife conization, laser conization, and loop electrosurgical excisional procedure (LEEP) were prospectively compared with respect to treatment reliability, effectiveness, and safety. One hundred ten women with CIN1-2 and the squamnocolumnar junction not seen or CIN3 at the original diagnosis were randomized to treatment with cold knife conization (n = 37), laser conization (n = 37), or LEEP (n = 36). All three treatments were performed with local anesthesia on an outpatient basis. The mean age, histologic features (original and histology of the conization), endocervical involvement, and ectocervical extension were similar in the three groups. Blood loss and operating time were less (P < 0.01) in the LEEP group (5.4 cc of mean blood loss and 5.4 min mean duration time) than in the two other groups (16.2 cc and 14.0 min for cold knife conization, 21.5 cc and 15.6 min for laser conization). Volumes of the cones were evaluated: LEEP cones and laser cones were smaller than the cold knife cones (P < 0.001). During the pathological review of the conization, the major problem was difficulty in evaluating the lesion and its margins due to the coagulation induced by the laser or the LEEP. This alteration was present in 53% of the LEEP conization specimens and in 51% of the laser conization specimens. In the majority of the cases the coagulation was mild, but in one case (LEEP group) and in two cases (laser group) the conization was totally altered by the coagulation, and in 31% of all the LEEP conizations and 38% of all the laser conizations, evaluation of the entire margin was not possible due to coagulation of the tissue. During postoperative follow-up, the number of complications was the same in the three groups (two episodes of post-operative bleeding in each of the three groups). Two months after the treatment the cervix was evaluated: the os was diminished in the cold knife group compared to the two other groups and as a result, the squamnocolumnar junction was not seen in entirety in 50% of cold knife cases, in 19% of LEEP cases, and in 20% of laser cases. These results suggest that in our hands: (1) laser conization is relatively costly and time consuming and alters the tissues significantly, and (2) the choice between cold knife and LEEP is more difficult--cold knife gives a sample adequate for histological evaluation (including evaluation of the margins), while the LEEP procedure is technically easier and less time consuming but sometimes induces electrocautery artifact so that evaluation of the margins is not possible.

Adult↗
PubMed1994

Pulmonary deposition of aerosolised pentamidine using a new nebuliser: efficiency measurements in vitro and in vivo.

The therapeutic efficacy of nebulised pentamidine in the prophylaxis of Pneumocystis carinii pneumonia (PCP) depends on the absolute pulmonary deposition of the drug. We studied the performance of a new nebuliser (Pentasave) by comparison both in vitro and in vivo with a standard nebuliser (Respirgard II). In vitro, deposition of pentamidine labelled with technetium-99m human serum albumin was measured indirectly by capturing inhaled particles on an absolute filter and measuring radioactivity with a gamma camera. The nebulisers were initially assessed with a pentamidine dose of 100 mg in 5 ml at 44 psi and an air flow of 10 l/min for Respirgard II and 16 l/min for Pentasave. Nebuliser output, expressed as the percentage of the initial nebuliser radioactivity captured by the inhalation filter, was 15% +/- 2% (mean +/- SD) for Respirgard II, and significantly increased to 23% +/- 3% for an initial version and to 33% +/- 2% for the final version of Pentasave. Measurements with a gamma camera in a group of ten patients with human immunodeficiency virus infection were made in vivo. The results revealed that pulmonary drug distributions are good using both Respirgard II and Pentasave. The literature reports that once-monthly pulmonary deposition of 9 mg pentamidine seems enough to produce prophylactic effects against Pneumocystis carinii. We measured pulmonary pentamidine deposition of 20.22 +/- 4.31 mg (mean +/- SD) using Respirgard II (with 300 mg in 5 ml) and of 16.00 +/- 7.18 mg using Pentasave (with 150 mg in 6 ml). These findings show that the therapeutic dose of pentamidine (9 mg) was widely exceeded with both nebulisers. Further investigations might demonstrate that about 200 mg and 125 mg pentamidine for Respirgard II and Pentasave, respectively, will achieve a pulmonary deposition of therapeutic dose, allowing significant savings in terms of drug and expense.

Administration, Inhalation↗
PubMed1994

Hydromorphone patient-controlled analgesia (PCA) after coronary artery bypass surgery.

We conducted a study to compare the effectiveness of patient-controlled analgesia (PCA) technique to conventional analgesic therapy (CAT) after coronary artery bypass graft (CABG). The PCA group received hydromorphone 0.1 mg.hr-1 basal infusion and bolus doses of 0.2 mg Q 5 min (maximum 1.2 mg.hr-1) while the CAT group received morphine 2.5 mg iv Q 30 min prn until extubation followed by prn meperidine 1 mg.kg-1 im Q 4 hr or acetaminophen 325 mg with codeine 30 mg po (1 or 2 tablets) when oral intake was possible. The degree of pain was assessed using a Visual Analogue Scale (VAS) starting after extubation and every 6-8 hr for the next 60 hr. Holter monitoring was initiated one hour after patient arrival in the Intensive Care Unit (ICU) and continued for 72 hr. Other measured variables were pulmonary function, sedation, side effects and total opioid requirements. Results show that the day-to-day VAS pain score decreased in the PCA group (P < 0.001) while it remained unchanged in CAT patients. The PCA patients had lower VAS pain scores at extubation (P < 0.05). During the third postoperative day, the PCA group had a lower VAS pain score, a lower incidence of severe pain defined as a score > 5 on the VAS scale, and a reduced incidence of myocardial ischaemia (P < 0.01). However, there was no difference in the duration, severity, area under the curve (AUC), or heart rate during ischaemic events. Postoperative pulmonary function was abnormal in both groups (NS) with minimal recovery by the fourth day.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesia↗
PubMed1994

Hemodynamic and pharmacodynamic comparison of doxacurium and high-dose vecuronium during coronary artery bypass surgery: a cost-benefit study.

Doxacurium (DOX), a new nondepolarizing neuromuscular blocking drug (NMBD), was compared in a randomized, double-blind fashion to high-dose vecuronium (VEC) in 60 coronary artery bypass grafting (CABG) patients. A third group of 15 patients older than 70 years of age (DOX-70) was added to compare the effects of DOX to VEC in the older population. Endpoints of the study were hemodynamic stability, ease of ventilation and intubation, anesthesiologist's satisfaction, drug interventions to correct hemodynamic instability, and total cost of the drug. Anesthesia was induced with fentanyl (30 micrograms/kg) along with the NMBD (DOX 80 micrograms/kg, VEC 400 micrograms/kg) over a 2-minute period. Following induction, heart rate (HR) and mean arterial pressure (MAP) were decreased (P < 0.01) in all groups. Tracheal intubation caused the HR to return to baseline in the DOX-70 group. There was no difference in central venous pressure, pulmonary artery occlusive pressure, cardiac index, systemic vascular resistance, and drug intervention for DOX and VEC. None of the patients had evidence of myocardial ischemia. There was a statistically significant but clinically irrelevant decrease in central venous pressure and systemic vascular resistance in the DOX-70 group. The durations of the induction and maintenance doses of DOX were similar in the younger and older patients. Although the intubating dose of VEC had a faster onset of action, this had no effect on the ease of ventilation, conditions for tracheal intubation, and overall anesthesiologist satisfaction. The total cost for each NMBD was not different.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗