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Biomedical subjects

J Stewart

Publications and source records attributed to J Stewart.

At least 253 records · Page 14Linked to original sources
PubMed1995

Manitoba targets patient overuse as it tackles abuse of health care system.

Manitoba has begun to respond to overuse of its health care system by forcing people who visit too many doctors or pharmacies to limit their use to one doctor and one drugstore. The province reviewed the records of patients who made more than 67 office visits in a year and/or saw more than 12 physicians annually. The heaviest user made 247 office visits to 71 different physicians in 1 year. The new restriction applies to about 28 patients. The move is expected to save the province $116,000.

Cost Control↗
PubMed1995

Russian family physicians try to develop an identity in specialist-oriented country.

Russia is in the process of reforming its medical system to place more emphasis on family medicine. Currently, most of the emphasis is on specialization and family doctors are considered little more than referral agents to specialists. Last fall, three Russian doctors with an interest in family medicine attended a conference in Winnipeg. Although they hope to learn from Canadian colleagues, they also think that Canada might be able to learn from Russian experience in the health-promotion field.

Canada↗
PubMed1995

Ventral tegmental area opioid mechanisms and modulation of ingestive behavior.

In this paper we report on the effects of intra-VTA infusion of opioid agonists on rat ingestive behavior in a variety of experimental contexts. When the animals were tested outside of their home cages surrounded only by food-pellets (Experiment 1), the injection of the mu-opioid agonist DAMGO, but not the kappa-opioid agonist U-50,488H, into the ventral tegmental area facilitated food-related behaviors, decreasing the latency to feed and increasing the number of interactions with food. When, as in Experiment 2, gnawable objects and a drinking tube were also available, intra-VTA DAMGO gnawing and drinking behaviors, whereas the effects on feeding were negligible. These effects intra-VTA DAMGO increased were greatly enhanced in rats that underwent repeated treatments with amphetamine. On the other hand, when food-related behaviors were studied in a home-cage, where access to the food supply was achieved by entry into a tunnel, latency to feed and total food-intake were not enhanced in tests made during either the dark or the light phase (Experiment 3 and 4). This was true whether powdered standard lab chow or a highly palatable food was available. It appears that when a number of alternative incentive stimuli are available, increases in dopamine transmission such as that induced by intra-VTA DAMGO may ultimately have the effect of interfering with behavior normally directed primarily to one of these stimuli, by enhancing the salience of others. These effects bears some resemblance to the effects of tail-pinch and electrical brain stimulation of the medial forebrain bundle-lateral hypothalamic area on the responses to natural incentive stimuli.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1995

Islet cell mass and predisposition to non-insulin-dependent diabetes mellitus.

A research team at the University of Manitoba's Faculty of Medicine is searching for the genetic marker that determines pancreatic islet cell mass. If this research is successful it may be possible to identify people with a genetic predisposition to non-insulin-dependent diabetes mellitus. Little is known about islet cells, although it is believed that they achieve peak mass in the neonatal period or even in utero. Led by Dr. Liam Murphy, the research team is looking at chromosome 6 for the homeobox genes that control foregut and pancreatic development. They are at the stage of cross-breeding mice in order to follow a trend in their genetic make-up. Once the determinants of islet cell mass in mice are found the search for the corresponding genes in humans can begin. Their research is expected to take several years to complete.

Animals↗
PubMed1995

Evaluation of antigen and antibody detection in urine specimens from children with congenital human cytomegalovirus infection.

Fetal infection with human cytomegalovirus (HCMV) is the leading viral cause of brain damage among newborns at birth or later in life. Efforts to screen newborns routinely for shedding of the virus by immunoassay have been hampered by inhibitors in urine, reportedly the host protein beta2-microglobulin (beta 2m). An enzyme-linked immunosorbent assay (ELISA) was developed for the detection of HCMV antigen in which the reactivity was not affected by the presence of beta 2m, but nevertheless inhibition was observed when urine samples with high levels of virus were tested. The presence of antibodies to HCMV was demonstrated in these urine samples by antibody ELISA and immunoblot using the major antigenic protein of HCMV (pp150) expressed in Escherichia coli; this offers an alternative explanation for the inhibition in ELISA. The presence of HCMV antibodies correlated significantly with congenital HCMV infection (as detected by tissue culture isolation of virus from urine samples of newborns), especially with asymptomatic cases (sensitivity 70%; specificity 94%). The data indicate a local (renal) immune response to HCMV in congenitally infected children, which may have future diagnostic applications.

Adult↗
PubMed1995

Temporal factors in the effect of restraint stress on morphine-induced behavioral sensitization in the rat.

The role of associative factors in the effect of 15 min/day of restraint stress on morphine-induced behavioral sensitization was examined. Male rats were initially given seven systemic (10 mg/kg, IP) or intraventral tegmental area (VTA, 5 micrograms/side) [corrected] injections of morphine, and were exposed to restraint, either just prior to drug injection (Paired-Stress) or 24 h after injection (Unpaired-Stress), or to no restraint (Control). In subsequent tests for behavioral sensitization to low doses of morphine (0.75 or 3.0 mg/kg, IP), animals in the Paired-Stress condition were more active than animals in the Unpaired-Stress or Control conditions. These results indicate that temporal and possibly associative factors may contribute to stress-induced changes in sensitization to the behavioral activating effects of opioids.

Animals↗
PubMed1995

Stress reinstates heroin-seeking in drug-free animals: an effect mimicking heroin, not withdrawal.

Exposure to 10 min of footshock stress (1 mA; 0.5 s on, with a mean off period of 40 s) reinstated heroin-seeking behavior in heroin-experienced, drug-free rats after many sessions of extinction and up to 6 weeks after last exposure to heroin. In reinstating the behavior, the footshock mimicked the effect of a non-contingent priming infusion of heroin (50 micrograms/kg). By contrast, the aversive state of acute opioid withdrawal induced by injection of the opioid receptor antagonist naltrexone (5 mg/kg, SC), following an acute injection of morphine (10 mg/kg, SC), had no effect on heroin-seeking behavior. In a second experiment it was shown in drug naive animals that these parameters of footshock increased dopamine overflow in the nucleus accumbens, a terminal region of the mesolimbic dopamine system implicated in the reinforcing effects of drugs. Similarly, dopamine overflow was increased by an injection of 10 mg/kg morphine, SC, an effect that was reversed by an injection of 5 mg/kg naltrexone given 40 min after to induce the withdrawal condition. A possible interpretation of the present results is that stressors can reinstate drug-taking behavior by activating neural systems in common with those activated by heroin.

Animals↗
PubMed1995

Micronucleus formation induced by three polycyclic aromatic hydrocarbons in rat bone marrow and spleen erythrocytes following intratracheal instillation.

Benz[a]anthracene (BA), dibenz[a,h]anthracene (DBA) and dibenzo[a,i]pyrene (DBP) are polycyclic aromatic hydrocarbons (PAHs) found in incomplete combustion products of fossil fuels, coal tar, and other organic materials. Workers in related industries may be exposed to these chemicals by inhalation. The information related to the potential health hazards of these chemicals to the exposed workers, however, is very limited. In the present study, micronucleus (MN) formation in rat bone marrow and spleen polychromatic erythrocytes (PCEs) was determined following three intratracheal instillations within a 24-h period with either BA, DBA or DBP. Three doses with five rats per dose were used for each chemical. Bone marrow and spleen cells were harvested 24 h after the first dosing. Results showed that the order of toxicity for the three PAHs was DBP > DBA > BA. BA induced MN in a dose-related manner in both bone marrow and spleen PCEs at doses above 25 mg/kg. DBA caused significant increases in the frequencies of MN in both spleen and bone marrow PCEs at the dose of 8.5 mg/kg or higher. At 10 mg/kg, DBP significantly increased MN frequency in spleen PCEs, but the increase in bone marrow PCEs was not significantly different from the control. These results indicate that: (1) all three PAHs studied are absorbed through the respiratory tract and their genotoxic metabolites reach the bone marrow and/or spleen; (2) except for DBP which does not induce MN in the bone marrow, all three PAHs induced MN in both bone marrow and spleen PCEs; and (3) the sensitivity of the spleen to the three PAHs is comparable to or higher than that of the bone marrow.

Air Pollutants, Occupational↗
PubMed1995

Desflurane controls the hemodynamic response to surgical stimulation more rapidly than isoflurane.

STUDY OBJECTIVE: To compare the control of hemodynamic response to surgical stimulus of desflurane to that of isoflurane. DESIGN: Prospective randomized study. SETTING: Operating room of a major U.S. teaching hospital. PATIENTS: 59 ASA status I, II, and III patients 18 to 80 years of age and were undergoing orthopedic or intra-abdominal surgical procedures of 1 or more hours in duration. INTERVENTIONS: Group 1 (n = 29) received desflurane in oxygen (O2) for their surgical procedure. Group 2 (n = 30) received isoflurane in O2 for their surgical procedure. Thiopental sodium 4 mg/kg and fentanyl 3 micrograms/kg provided induction; vecuronium 0.1 mg/kg facilitated intubation. Prior to incision the volatile anesthesia drug was titrated to maintain systolic blood pressure (SBP) within 20% of preinduction (baseline) values. Any time after incision, an SBP increase greater than 20% of baseline was treated with a 30% increase in inspired anesthetic concentration for 3 minutes, or until SBP was within 10% of baseline. Another three 30% increases were allowed at 3 minute intervals to return SBP to 10% of baseline. If four 30% increases did not return SBP to 10% of baseline, additional fentanyl up to 5 micrograms/kg or labetalol in 5 mg increments was given. MEASUREMENTS AND MAIN RESULTS: Measurement of hemodynamics and anesthetic concentration occurred every 2 minutes prior to skin incision and every 5 minutes thereafter. Measurement of hemodynamics and anesthetic concentration occurred every minute during treatment of blood pressure (BP) response to surgical stimulus. Desflurane allowed for more rapid control of BP response to surgical stimulus median 2 minutes (range 1 to 12 minutes) for desflurane versus 6 minutes (range 1 to 12 minutes, p = 0.011). The desflurane group required fewer 30% incremental anesthetic increases than the isoflurane group (1.8 versus 2.5, p = 0.016) to control increased SBP. End tidal/inspired drug concentration ratios were closer to unity in the desflurane patients both before (0.94 versus 0.80) and after (0.86 versus 0.70) changes in drug concentration to treat increased SBP. CONCLUSIONS: Anesthetic depth can be more rapidly titrated with desflurane compared to isoflurane. Alveolar/inspired concentration ratio approaches unity more rapidly with desflurane anesthesia.

Adolescent↗
PubMed1995

Changes in the neonatal gonadal hormonal environment prevent behavioral sparing and alter cortical morphogenesis after early frontal cortex lesions in male and female rats.

The effects of perinatal exposure to testicular hormones were studied in male and female rats given medial prefrontal lesions (PFC) on Postnatal Day 7. Hormonally intact rats with PFC lesions showed recovery of performance of the Morris water task but no recovery on a forelimb reaching task. Recovery was abolished in both males gonadectomized at birth and in females given testosterone at birth. Male rats with PFC lesions showed an increase in pyramidal cell spine density. This was blocked in gonadectomized animals. In contrast, female rats with PFC lesions showed an increase in dendritic arbor. This was reduced by perinatal testosterone. Interference with the gonadal hormonal environment reduced the brain's ability to compensate for the effects of early cortical lesions.

Animals↗
PubMed1995

The ontogeny of class-regulation of CD4+ T lymphocyte populations.

The differential class-regulation of CD4+ T lymphocyte populations is believed to play a major role in determining the qualitative behaviour of the immune system, and in the fate of immune responses in particular. In this article we propose a model for the dynamics of the Th1 and Th2 subpopulations. We put forward the concept of an 'antigenic niche' which allows us to postulate that the key feature underlying the regulation of Th differentiation pathways is the population dynamics of the lymphocytes themselves. Using this model we are able to account for a number of well established experimental observations which were hitherto apparently unrelated and poorly understood. This suggests that our simplified model might be capturing some essential features of the immune system.

Animals↗
PubMed1995

Reflective midwifery practice: facilitating midwives' practice insights using a distance education reflective practitioner model.

A study was undertaken to evaluate a reflective practitioner model with midwives, who self-selected into the project when they were studying the Bachelor of Health Science (Nursing) unit NR278, Advanced Nursing Practice, Midwifery. The theoretical assumptions that influenced the research were those forwarded by Schon (1983) and Boud, Keogh and Walker (1985), who argued that practitioners are often unaware of the sophisticated knowledge they have regarding the intricacies of their practice, but that this personal knowledge can be make explicit through reflective processes. The aim of the study was to research the use of a distance education reflective practitioner process that encouraged midwives to examine their practice with a view to making changes where necessary. All the research objectives were met to some extent, although each experience of the research process was particular to the individual participant. Analysis consisted of: interpretation of the participant's insights into their individual experiences; the researcher's interpretations of participant's experiences; and collective themes arising out of the research. This paper concentrates mainly on the participant's insights into their individual experiences of practising midwifery, using a reflective practitioner model.

Education, Nursing, Baccalaureate↗
PubMed1995

Subacute enlarging cerebral hematoma from amyloid angiopathy: case report.

We report the case of a 74-year-old woman who, during a 36-hour period, developed progressive, focal neurological deficits and eventual coma associated with a spontaneously enlarging intraparenchymal hematoma resulting from cerebral amyloid angiopathy. The subacute, progressive enlargement of the hematoma, confirmed by serial computed tomographic scans, supports the hypothesis that hematomas enlarge in amyloid angiopathy as a result of the replacement of the contractile elements of the arterial wall by noncontractile amyloid protein. This interference with vasoconstriction, the first phase of hemostasis, may be supplemented by local endothelial dysfunction causing alterations in the chemical mediators of hemostasis, thereby promoting hemorrhage and hematoma enlargement.

Acute Disease↗
PubMed1995

Development of a customizable universal digital hearing aid.

This paper presents the development of a digital binaural hearing aid using Texas Instruments' floating point TMS320C3X digital signal-processing chip. The device is referred to as the Customized Universal Digital Listening System (CUDLS). CUDLS uses a wide bandwidth (up to 16 kHz) and incorporates speech enhancement (noise reduction) as an integral part of the device. It is capable of sampling up to two input speech channels at a variable sampling rate. We are currently using a sampling rate of 20 kHz for each channel. We have developed our own customized hardware and software to implement CUDLS in real time with zero processing delay. The system has been designed to make it easy for the therapist to modify its features.

Correction of Hearing Impairment↗
PubMed1994

Development of an idiotypic network in shape space.

Based upon the shape-space formalism, a model of an idiotypic network including both bound and free immunoglobulins is simulated. Our point of interest is the network development in the context of self antigens. The investigations are organized around simulations initiated by various spatial configurations of antigens; the behavior of the system with respect to antigens is analyzed in terms of morphogenetic processes occurring in the shape space. For certain values of the parameters, the network expands by traveling waves. The resulting spatial pattern is a partition of the shape space into zones where introduction of an antigen entails an infinite growth of the clones binding to it, and into zones where, on the contrary, the anti-antigen idiotypes decrease. Among the parameter combinations tested, some produce a partition that remains static whereas others produce a partition that changes in time. For other values of the parameters, the patterns generated do not partition shape space into zones; in these cases, it is observed that the system systematically explodes when an antigen is present.

Animals↗
PubMed1994

Hereditary non-polyposis colorectal cancer--morphologies, genes and mutations.

Mutations in a human homologue of the yeast DNA mismatch repair gene MSH2 (equivalent to bacterial MutS) cause the condition hereditary non-polyposis colorectal cancer (HNPCC). Cancers in HNPCC originate within benign neoplastic polyps termed adenomas. Adenomas are clonal and each may serve as a marker of a single initiating mutation. The progression of adenomas is marked by increasing size, dysplasia and villosity. These characteristics can be taken as the morphological counterparts of the stepwise accumulation of mutations implicating oncogenes and tumour suppressor genes. The aim of this study was to link the morphogenesis of hereditary colorectal cancer with recent insights into the role of DNA mismatch repair genes. The frequency and anatomical distribution of adenomas in at-risk members of HNPCC families was the same as in an autopsy population. This suggests that the HNPCC gene does not initiate the process of neoplastic transformation. On the other hand, adenomas in at-risk members of HNPCC families were more likely to show villosity (p < 0.001), high grade dysplasia (p = 0.002) and probably increased size (p = 0.15). These findings are consistent with the observation that the HNPCC gene causes DNA replication errors to develop and accumulate within neoplastic but not normal tissues. The effect of the HNPCC gene is to accelerate the progression of adenoma to carcinoma, but not to initiate adenoma development.

Adenoma↗
PubMed1994

Rethinking "shape space": evidence from simulated docking suggests that steric shape complementarity is not limiting for antibody-antigen recognition and idiotypic interactions.

The concept of "shape space" is based on the assumption that the relevant properties of individual molecules can be adequately specified by a finite list of N parameters; and that cij, the affinity between molecules i and j, can be specified by an equation of the form: cij = f(xi, xj), where xi and xj are N-dimensional vectors representing the absolute positions of molecules i and j in an objective, referential "shape space", and f is an appropriate function. We have performed simulated docking of the combining sites of immunoglobulin molecules, based on their crystallographic structures. The results suggest that shape complementarity cannot account for the specificity of idiotypic interactions, since in the simulations each pair of docked proteins had a buried surface area as great as that occurring in known complexes. It therefore seems likely that the atomic interactions accounting for the specificity of immunoglobulin recognition are highly relational. This casts doubt on the basic assumptions underlying the shape-space concept, at least in the simple form hitherto used in theoretical modelling of the immune system. In order to be realistic, the dimensionality N would have to be high (more than 20), and the function f would be irregular and discontinuous. Alternatively, if the equation cij = f(xi, xj) is interpreted as a purely formal construction in an abstract "inversion space", its validity is entirely relative to the empirical affinity matrix on which the construction is based. We conclude that at present there is no sure way of adequately characterizing the internal structure of idiotypic affinity matrices; and that models of the immune system should therefore aim at being generic and robust with respect to the structure of the idiotypic affinity matrices of unselected immunoglobulins.

Algorithms↗