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Biomedical subjects

M Roy

Publications and source records attributed to M Roy.

At least 73 records · Page 4Linked to original sources

A real time quantitative PCR-based method for the detection and quantification of simian virus 40.

A real time quantitative PCR-based simian virus 40 (SV40) detection and quantification method has been developed. This method takes advantage of the 5' to 3'-exonuclease activity of Taq DNA polymerase and utilizes the PRISM 7700 sequence detection system of PE Applied Biosystems for direct monitoring of PCR product accumulation through a dual-labelled fluorogenic probe. This method provides accurate, precise and reproducible quantification of SV40 DNA over a linear dynamic range of at least 100,000-fold with a minimum detection level of 6.4 copy equivalents/microL of SV40 viral particle in test samples. The sample preparation procedure employed allows for efficient and consistent recovery of SV40 DNA from test samples. High concentrations of protein and cellular DNA presenting in test samples have been demonstrated to have no impact on SV40 quantification. This method offers significant advantages over other PCR methods and cell-based infectivity assays currently available for SV40 detection and quantification. The availability of this method should greatly facilitate the pathogenic investigation of SV40, as well as viral clearance evaluations required for the development of new biological products.

DNA, Viral↗

Comparison of the hemodynamic effects of sevoflurane anesthesia induction and maintenance vs TIVA in CABG surgery.

PURPOSE: To compare the hemodynamic effects of sevoflurane when used for induction and maintenance of anesthesia with a total intravenous technique in patients with known coronary artery disease (CAD). METHODS: Thirty patients undergoing elective coronary artery bypass graft (CABG) were randomly allocated to receive either sevoflurane (S group, n = 15) at a minimal concentration of 4% in oxygen for induction and at 0.5-2 MAC end-tidal concentration for maintenance, or a total intravenous technique (T group, n = 15) consisting of midazolam for induction and propofol for maintenance. In both groups, anesthesia was supplemented with sufentanil and muscle relaxation with cis-atracurium. Hemodynamic measurements included systemic and pulmonary pressures, heart rate, mixed venous oxygen saturation and cardiac output at the following times: pre-induction, 7 and 25 min post-induction, chest closure, one hour after surgery and pre and post tracheal extubation. RESULTS: More patients in the S group (8/15) presented bradycardia in the induction period (T:2/15) (P = 0.05). During maintenance of anesthesia, treatment of hypertension was more frequent in the T group (12/15) than in the S group (6/15) (P = 0.025). All other parameters were comparable. CONCLUSION: Induction of anesthesia in patients with CAD, VCRII with sevoflurane supplemented by sufentanil provided hemodynamic responses comparable with those of TIVA although bradycardia was observed more often with sevoflurane. Intraoperative control of systemic blood pressure was achieved with fewer interventions with a sevoflurane/sufentanil maintenance than with a propofol/sufentanil technique in CABG surgery.

Aged↗

Neuronal apoptosis in acute necrotic insults: why is this subject such a mess?

It is now recognized that necrotic neurological insults often trigger apoptosis in a subset of neurons. It is also now apparent that such apoptosis rarely matches the 'classical' apoptosis seen during development or the physiological turnover of cells outside the nervous system. As a result, the view has emerged that the 'apoptosis-like' changes that follow necrotic insults represent a different phenomenon, which is on a vague continuum with the necrotic features of cell death. We suggest that apoptosis following neurological insults is, in actuality, mechanistically identical to classical apoptosis. However, the atypical apoptotic endpoints that are observed are inevitable, given the way in which insult-triggered apoptosis is likely to have evolved.

Acute Disease↗

A two-center study evaluating the hemodynamic and pharmacodynamic effects of cisatracurium and vecuronium in patients undergoing coronary artery bypass surgery.

OBJECTIVE: To determine the hemodynamic and pharmacodynamic effects of rapid bolus administration of cisatracurium compared with vecuronium. DESIGN: A randomized, prospective, double-blind study. SETTING: Tertiary-care university hospitals. PARTICIPANTS: Seventy-nine adult patients with diagnosed coronary artery disease (CAD). INTERVENTION: Elective coronary artery bypass graft surgery (CABG). MEASUREMENTS AND MAIN RESULTS: Patients were randomly divided into four groups. Patients received a rapid bolus of two or four times the 95% peak depression of twitch (ED95) of either cisatracurium (groups 1 and 2) or vecuronium (groups 3 and 4). Three minutes after a midazolam induction, all patients received a rapid bolus administration of either study drug. Maintenance of anesthesia was with a standardized propofol-sufentanil-oxygen anesthetic. Patients were monitored with radial and pulmonary artery catheters and electromyography. End points of the study were hemodynamic stability at induction, after bolus administration of study drugs, and after intubation; the quality of intubating conditions; drug interventions to correct hemodynamic instability; the onset, duration, and recovery of neuromuscular function; and drug cost. Mean arterial pressure (MAP) and heart rate (HR) decreased in a similar proportion in all four groups after induction while, following study drug administration, MAP and HR did not change significantly. Both cisatracurium groups required more boluses to maintain neuromuscular block, but spontaneous recovery rates were faster. Both agents, but cisatracurium to a lesser degree, showed increased duration with repeated maintenance doses. Both agents afforded good to excellent intubating conditions, but the cost of cisatracurium was significantly less. CONCLUSION: The authors conclude there is no evidence of a hemodynamic difference between the two neuromuscular blocking drugs (NMBDs). There are some clinical and cost advantages in favor of cisatracurium.

Adolescent↗

The molecular basis for protein kinase A anchoring revealed by solution NMR.

Compartmentalization of signal transduction enzymes into signaling complexes is an important mechanism to ensure the specificity of intracellular events. Formation of these complexes is mediated by specialized protein motifs that participate in protein-protein interactions. The adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase (PKA) is localized through interaction of the regulatory (R) subunit dimer with A-kinase-anchoring proteins (AKAPs). We now report the solution structure of the type II PKA R-subunit fragment RIIalpha(1-44), which encompasses both the AKAP-binding and dimerization interfaces. This structure incorporates an X-type four-helix bundle dimerization motif with an extended hydrophobic face that is necessary for high-affinity AKAP binding. NMR data on the complex between RIIalpha(1-44) and an AKAP fragment reveals extensive contacts between the two proteins. Interestingly, this same dimerization motif is present in other signaling molecules, the S100 family. Therefore, the X-type four-helix bundle may represent a conserved fold for protein-protein interactions in signal transduction.

Amino Acid Sequence↗

Ondansetron is more effective than metoclopramide for the treatment of opioid-induced emesis in post-surgical adult patients. Ondansetron OIE Post-Surgical Study Group.

Nausea and vomiting are common side effects of opioids administered for pain control. This double-blind, randomized, parallel-group study evaluated the anti-emetic efficacy and tolerability of single intravenous (i.v.) doses of ondansetron 8 mg, ondansetron 16 mg and metoclopramide 10 mg in the treatment of opioid-induced emesis. Adult patients undergoing low emetogenic surgical procedures, using a standardized anaesthesia regimen were assessed for 24 h following administration of study anti-emetic to treat established post-surgical opioid-induced emesis. A total of 4511 patients were enrolled of whom 1366 experienced opioid-induced emesis and received randomized study medication. Ondansetron 8 mg and 16 mg were significantly better than metoclopramide 10 mg (P < 0.05) for both complete control of emesis, complete control of nausea and other efficacy measures. There were no significant differences between the two ondansetron groups. All three treatments were well tolerated. In conclusion, this large, multicentre study demonstrates that ondansetron is more effective than metoclopramide in the treatment of opioid-induced emesis following administration of post-surgical opioids to control pain.

Adolescent↗

[Neurologic sequelae secondary to acute lithium poisoning].

OBJECTIVE: To review the literature on the permanent neurological sequelae resulting from acute lithium poisoning. METHOD: Sixty-six articles were reviewed in English and in French. They were accessed through Medline and cover the period from 1968 to 1997. RESULTS: Fifty-nine case studies were broken down into 3 groups: lithium intoxications without a neuroleptic that has provoked a cerebellar syndrome; those in which there was a neuroleptic; and those with diverse neurological consequences, with or without a neuroleptic. CONCLUSIONS: Lithium has an intrinsic toxicity for the central nervous system and provokes a tropism specific to the cerebellum. The association with neuroleptics appears to increase toxicity as well as some associated factors, including infections and the rapid correction of the lithium level in the blood. We discuss the psychopathological mechanisms invoked to explain lithium's neurotoxicity.

Antipsychotic Agents↗

Variation at 4 short tandem repeat loci in 8 population groups of India.

We have determined the nature and extent of variation at 4 STR loci (CSF1P0, TPOX, TH01, VWA) in 8 caste and tribal population groups of eastern and northern India. Large differences in allele frequencies among the groups were found. Average heterozygosities in all populations were high (approximately 80%). The overall extent of gene differentiation among the 8 groups was high (GST = 0.04). The nature of genomic affinities based on these 4 STR loci does not completely agree with our earlier finding based on classical genetic markers that geographic proximity of habitat has a greater influence on genetic similarity between populations than sociocultural proximity does.

Developing Countries↗

Sarcoidosis presenting in infancy: a rare occurrence.

Sarcoidosis is infrequent in children. Clinical features of sarcoidosis occurring in children 8-15 years old include pulmonary, lymphnodes and ocular involvement. The picture is similar to that of adult-sarcoidosis. Sarcoidosis in infants, however, is rare and it differs from the adult disease. Sarcoidosis occurring in infancy has features clinically similar to that of juvenile rheumatoid arthritis. The case presented here is that of an infant who developed sarcoidosis at the age of 3 months. Her illness had all the features of a multisystem illness except for the hilar or parenchymal lung involvement. Because of the complicated and unusual illness the diagnosis of sarcoidosis was not established till the child was five years old. She received corticosteroids and immunosuppressive treatment in varying doses for a long time. Now at the age of 18, the patient's disease seems to have undergone a complete remission.

Adrenal Cortex Hormones↗

Genomic amplification of a decoy receptor for Fas ligand in lung and colon cancer.

Fas ligand (FasL) is produced by activated T cells and natural killer cells and it induces apoptosis (programmed cell death) in target cells through the death receptor Fas/Apol/CD95. One important role of FasL and Fas is to mediate immune-cytotoxic killing of cells that are potentially harmful to the organism, such as virus-infected or tumour cells. Here we report the discovery of a soluble decoy receptor, termed decoy receptor 3 (DcR3), that binds to FasL and inhibits FasL-induced apoptosis. The DcR3 gene was amplified in about half of 35 primary lung and colon tumours studied, and DcR3 messenger RNA was expressed in malignant tissue. Thus, certain tumours may escape FasL-dependent immune-cytotoxic attack by expressing a decoy receptor that blocks FasL.

Adult↗

Operative laparoscopy prior to a pelvic exenteration in patients with recurrent cervical cancer.

INTRODUCTION: Selecting out the true candidates for a pelvic exenteration frequently poses a difficult clinical dilemma in patients with recurrent cervical cancer after radiation therapy. Despite very thorough preoperative investigation, inoperable disease is discovered at the time of laparotomy in up to 60% of cases. SUBJECTS AND METHODS: In this retrospective analysis, we report the use of operative laparoscopy in 13 patients with either biopsy proven locally recurrent cervical cancer (N = 9) or with clinically suspected tumor recurrence (N = 4). All have previously received radical radiation therapy. RESULTS: Patients' ages ranged from 36 to 79 years (median, 43). The median duration of the procedure was 150 min (range,50-200) and median blood loss was 50 cc (range, 50-200). The procedure was well tolerated in all patients. There was no intraoperative complication. One deep thrombophlebitis occurred postoperatively. The laparoscopic evaluation could not be completed in one case because of a large nonmobile uterine fibroid filling the whole pelvis. At laparoscopy, metastatic tumor was identified in 9 of 12 patients (75%). An unnecessary laparotomy was avoided in 8 of those 9 cases (one had a palliative exenteration). The most common site of metastasis was in the previously radiated pelvis (7/9). Three patients had a negative laparoscopy. Two had an exenteration and one had a transureteroureterostomy. At the time of laparotomy, none were found to have disease that would have been missed at laparoscopy. CONCLUSION: We conclude that operative laparoscopy may be a valuable additional step in the work-up and management of patients with locally recurrent cervical cancer. With experience in retroperitoneal surgery, the procedure can be carried out safely in previously radiated patients. We believe this approach can lower the number of unnecessary laparotomies, reduce the morbidity, and shorten the length of the postoperative recovery.

Adult↗

Experimental measurements of particle retention efficiency of filters used to prevent contamination in respiratory devices.

OBJECTIVE: Various types of filters have been designed to prevent cross contamination of ventilation and respiratory devices. The aim of this study was to experimentally measure the retention efficiency of four simple filters (antibacterial and antiviral and seven combined filters (antibacterial and antiviral plus heat and water exchangers). SETTING: The respiratory function testing (EFR) central department of a university teaching hospital. MEASUREMENTS AND RESULTS: The same aerosol test with a wide range of particle sizes (0.15 to 15 micrometers) was used to compare the retention efficiency of each filter used in various conditions. The particle sizes and the concentration of the aerosol were measured by a laser velocimeter. For all the filters studied, the retention efficiency was found to be higher than 99%. However some of them let large particles let through. CONCLUSION: These data, performed in vitro, should be assessed also by further clinical studies.

Air Pollutants↗

Pregnancies after radical vaginal trachelectomy for early-stage cervical cancer.

OBJECTIVE: The purpose of this study was to evaluate the role of fertility-preserving surgery in the treatment of early-stage cervical cancer. STUDY DESIGN: We retrospectively reviewed our first 30 patients treated by laparoscopic pelvic lymphadenectomy, followed by radical vaginal trachelectomy, from October 1991 to April 1998. RESULTS: The median age of the patients was 32 years (range 22-42 years); 15 were nulligravid and 19 nulliparous. Twenty cancers were at stage IB, 1 was at stage IA1, 7 were at stage IA2, and 2 were at stage IIA. The majority (18/30) were squamous. Two lesions were >2 cm in size, and only 4 had vascular space invasion. The median operative time was 285 minutes (range 155-455 minutes), median blood loss 200 mL (range 50-1200 mL), and median hospital stay 4 days (range 2-9 days). There were 4 intraoperative complications-2 attributed to the trachelectomy and 2 resulting from the lymphadenectomy. The current median follow-up time is 25 months (range 1-79 months). One patient had a recurrence in the left parametrium 18 months after vaginal radical trachelectomy and died of metastatic disease. The only 6 patients attempting pregnancy so far have succeeded: 4 have had healthy babies delivered by cesarean section at 39, 38, 34, and 25 weeks of gestation. Two are currently 33 and 8 weeks pregnant. CONCLUSION: Radical vaginal trachelectomy appears to be a valuable procedure in well-selected patients with early-stage cervical cancer. Successful pregnancies are definitely possible after this procedure. This new surgical technique warrants further careful evaluation to determine precise indications.

Adult↗

Prophylactic tranexamic acid and epsilon-aminocaproic acid for primary myocardial revascularization.

BACKGROUND: The efficacy of prophylactic epsilon-aminocaproic acid and tranexamic acid to reduce transfusions after primary myocardial revascularization was evaluated in a teaching hospital context. METHODS: Patients (n = 134) received either epsilon-aminocaproic acid (15-g bolus + infusion of 1 g/h), high-dose tranexamic acid (10-g bolus + placebo infusion), or normal saline solution in a double-blind fashion. Anticoagulation and conduct of cardiopulmonary bypass were standardized. RESULTS: Tranexamic acid and epsilon-aminocaproic acid produced a significant reduction in postoperative blood loss compared with placebo (median loss, 438 mL, 538 mL, and 700 mL, respectively). Transfusion of red cells was similar in all three groups. Nonetheless, the percentage of patients receiving hemostatic blood products was significantly decreased in the epsilon-aminocaproic acid group compared with the placebo group (20% versus 43%; p = 0.03). Both tranexamic acid and epsilon-aminocaproic acid significantly decreased total exposure to allogeneic blood products compared with placebo (p = 0.01 and p = 0.05, respectively), and this reduction was clinically important (median exposure, 2, 2, and 7.5 units, respectively). Fibrinolysis was inhibited significantly in both treatment groups. CONCLUSIONS: We conclude that either high-dose tranexamic acid or epsilon-aminocaproic acid effectively reduces transfusions in patients undergoing primary, elective myocardial revascularization.

Aminocaproic Acid↗

Expression of gamma-IFN responsive genes in scavenger receptor over-expressing monocytes is associated with xanthomatosis.

We have recently described an inherited over-expression of the macrophage scavenger receptor (SR) in blood monocytes from members of a kindred, only two of whom displayed extensive xanthomatosis. Using mRNA differential display we demonstrated abnormally high expression of the signal transducer and activator of transcription (STAT1alpha) in monocytes from the proband II-2. Expression of gamma-interferon inducible protein 10 (IP-10), a STAT1alpha-responsive gene and mediator of inflammatory response, was also abnormally expressed in the monocytes from II-2. Over-expression of both genes was restricted to monocytes from II-2 and was not observed in monocytes from the clinically unaffected family members, unlike that of SR. Gel retardation assays with THP-1 cell extracts identified gamma-IFN inducible DNA binding activity to three potential STATI DNA binding elements in the human IP-10 promoter region from nucleotides - 245 to - 188. Taken together these results suggest that gamma-interferon mediated cell activation is responsible for STAT1alpha-induced transcription of the IP-10 gene in THP-1 macrophages as well as in monocytes from II-2. Analysis of monocytes from familial hypercholesterolemic (FH) subjects, who frequently develop xanthomatosis, revealed a significant number of subjects with elevated STAT1alpha and IP-10 expression. Our data suggest that the inflammatory effects of gamma-IFN signaling could play a role in foam cell formation and xanthomatosis.

Adult↗