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Biomedical subjects

M Stewart

Publications and source records attributed to M Stewart.

At least 253 records · Page 14Linked to original sources

Detecting, preventing, and managing patients' alcohol problems.

OBJECTIVE: To examine Canadian family physicians' attitudes, beliefs, and practices regarding alcohol use and alcohol-related problems among their patients. DESIGN: A self-administered questionnaire mailed to a random sample of 2883 family physicians. The survey was conducted using a modified Dillman method. PARTICIPANTS: Canadian physicians in active office-based practice during 1989. Sample included certificated and noncertificated members of the College of Family Physicians of Canada, as well as non-members of the College. MAIN OUTCOME MEASURES: Perceived importance of various health-promotion behaviours; attitudes and beliefs about working with problem drinkers; current knowledge and practices regarding identifying and managing problem drinkers; and demographic characteristics. RESULTS: Respondents had a strong sense of role legitimacy in working with problem drinkers, but predominantly negative and pessimistic attitudes. Half the respondents felt they had failed in their work with problem drinkers. More physicians agreed on a psychosocial etiology for alcoholism than on a biological origin. Three quarters of respondents said they "almost always" ask patients about quantity and frequency of alcohol use, and just over one third "almost always" ask about problems related to drinking. Data also suggest doctors have relatively few patients with alcohol problems, and they need help in responding to such patients. CONCLUSION: Physicians need more training for their role in identifying and managing patients with alcohol problems.

Alcohol Drinking↗

Early indicators of hearing conservation program performance.

Retrospective analysis of initial audiograms from 21 hearing conservation programs (HCPs) revealed several statistical protocols capable of identifying HCPs of known performance. American National Standards Institute (ANSI) and Occupational Safety and Health Administration (OSHA) protocols clearly identified 3 HCPs known to have demonstrated excellent overall programs. ANSI and OSHA outcomes appeared equivalent in ability to provide early warnings of potentially unacceptable HCP practices.

Audiometry↗

Multiple lesions of intravascular papillary endothelial hyperplasia (Masson's lesions).

We recently encountered an elderly female patient with multiple, rapidly growing vascular lesions on her forearm. Histologic examination and immunoperoxidase studies were performed to identify cells present within the lesions. The growths proved to be intravascular papillary endothelial hyperplasia. Immunohistochemical studies showed these lesions to be proliferations of factor VIII+, factor XIIIa+, and CD34+ cells. Intravascular papillary endothelial hyperplasia lesions are growths that histologically can mimic angiosarcoma, especially when they are multiple. They appear to be proliferations of endothelial cells and also contain dermal dendrocytes. This finding raises the question as to the exact origin of the cells that give rise to these tumors.

Aged↗

Female patients' attitudes to mammography screening.

This study compares the attitudes of women who chose or chose not to have mammography screening. Women personally invited by their physicians to have mammography were more likely to go for screening. Those who did not go for screening were more afraid of medical tests and were less likely to want to know whether they had cancer.

Aged↗

Crystallization of the motile major sperm protein (MSP) of the nematode Ascaris suum.

We have obtained orthorhombic crystals (space group P2(1)2(1)2(1), a = 72 A, b = 78 A, c = 452 A) of the major cytoskeletal protein associated with the amoeboid motility of Ascaris sperm. These crystals diffract past 3.5 A and appear to be constructed from arrays of helical fibres of the major sperm protein. The fibres within the crystals appear to be closely analogous to those seen in vitro and in vivo.

Animals↗

Current source density analysis of the hippocampal theta rhythm: associated sustained potentials and candidate synaptic generators.

Single-electrode depth profiles of the hippocampal EEG were made in urethane-anesthetized rats and rats trained in an alternating running/drinking task. Current source density (CSD) was computed from the voltage as a function of depth. A problem inherent to AC-coupled profiles was eliminated by incorporating sustained potential components of the EEG. 'AC' profiles force phasic current sinks to alternate with current sources at each lamina, changing the magnitude and even the sign of the computed membrane current. It was possible to include DC potentials in the profiles from anesthetized rats by using glass micropipettes for recording. A method of 'subtracting' profiles of the non-theta EEG from theta profiles was developed as an approach to including sustained potentials in recordings from freely-moving animals implanted with platinum electrodes. 'DC' profiles are superior to 'AC' profiles for analysis of EEG activity because 'DC'-CSD values can be considered correct in sign and more closely represent the actual membrane current magnitudes. Since hippocampal inputs are laminated, CSD analysis leads to straightforward predictions of the afferents involved. Theta-related activity in afferents from entorhinal neurons, hippocampal interneurons and ipsi- and contralateral hippocampal pyramids all appear to contribute to sources and sinks in CA1 and the dentate area. The largest theta-related generator was a sink at the fissure, having both phasic and tonic components. This sink may reflect activity in afferents from the lateral entorhinal cortex. The phase of the dentate mid-molecular sink suggests that medial entorhinal afferents drive the theta-related granule and pyramidal cell firing. The sustained components may be simply due to different average rates of firing during theta rhythm than during non-theta EEG in afferents whose firing rates are also phasically modulated.

Action Potentials↗

Conditional expression and oncogenicity of c-myc linked to a CD2 gene dominant control region.

Over-expression of the c-myc gene is widely implicated in the genesis of lymphoid neoplasia, including tumours of the T-cell lineage. To study the effects of deregulated c-myc expression on T-cell development and oncogenesis, we sought to generate a transgenic mouse model in which c-myc expression was targeted specifically to the T-cell lineage. A plasmid construct containing a dominant control region (DCR) from the human CD2 locus linked 5' to the human c-myc gene was used to generate 2 lines of transgenic mice. Both strains developed thymic lymphoma at low frequency, but thymic development and peripheral T-cell numbers were otherwise apparently normal. Low tumour penetrance was consistent with the observed lack of stable CD2-myc transgene mRNA in tissues of healthy transgenic mice. In contrast, transgene RNA was detected in all malignant tumours as well as in early lymphomatous lesions. RNase protection analyses confirmed these findings and showed that the PI human c-myc promoter was active in all neoplastic tissues but not in the thymus or other tissues of healthy transgenic mice. Despite the low spontaneous tumour incidence, the presence of the transgene markedly and uniformly accelerated the onset of tumours after neonatal infection with Moloney murine leukaemia virus. All tumours were rearranged for T-cell receptor beta-chain genes and were of T-cell origin from their surface phenotype (Thy-1+, CD3+, CD4+/-, CD8+, sIg-). Virus-accelerated tumours contained clonal integrations of Moloney murine leukaemia virus, suggesting that proviral insertional mutagenesis may have played a role in tumour development. Analysis of several candidate myc-cooperating genes failed to reveal any rearrangements apart from a low frequency involving proviral insertion at the pim-1 locus. The CD2-myc mouse should therefore be a valuable system in screening for novel myc-collaborating genes involved in T-cell lymphoma.

Animals↗

[3H]p-aminoclonidine and [3H]idazoxan label different populations of imidazoline sites on rat kidney.

In the presence of RS-15385-197 to preclude binding to alpha 2-adrenoceptors, [3H]p-aminoclonidine labelled a low affinity high capacity site, (Kd = 127.6 +/- 19.7 nM, Bmax 978 +/- 172 fmol/mg protein) whereas [3H]idazoxan labelled a high affinity low capacity site (Kd = 1.66 +/- 0.28 nM, Bmax 45.3 +/- 11.4 fmol/mg protein). Clonidine and p-aminoclonidine showed moderate affinity for the site labelled by [3H]p-aminoclonidine, but low affinity for the site labelled by [3H]idazoxan, whereas idazoxan showed high affinity for [3H]idazoxan and low affinity for [3H]p-aminoclonidine binding. Naphazoline inhibited [3H]idazoxan in a biphasic manner suggesting that [3H]idazoxan may label an heterogeneous population of imidazoline sites. GTP inhibited [3H]idazoxan but not [3H]p-aminoclonidine binding. These results suggest that [3H]idazoxan labelled imidazoline I2 binding sites, whereas [3H]p-aminoclonidine labelled a novel subtype which showed marked differences to the imidazoline I1 binding site reported in bovine and human brainstem.

Adrenergic alpha-Antagonists↗

Procedural learning in Parkinson's disease and cerebellar degeneration.

We compared procedural learning, translation of procedural knowledge into declarative knowledge, and use of declarative knowledge in age-matched normal volunteers (n = 30), patients with Parkinson's disease (n = 20), and patients with cerebellar degeneration (n = 15) by using a serial reaction time task. Patients with Parkinson's disease achieved procedural knowledge and used declarative knowledge of the task to improve performance, but they required a larger number of repetitions of the task to translate procedural knowledge into declarative knowledge. Patients with cerebellar degeneration did not show performance improvement due to procedural learning, failed to achieve declarative knowledge, and showed limited use of declarative knowledge of the task to improve their performance. Both basal ganglia and cerebellum are involved in procedural learning, but their roles are different. The normal influence of the basal ganglia on the prefrontal cortex may be required for timely access of information to and from the working memory buffer, while the cerebellum may index and order events in the time domain and be therefore essential for any cognitive functions involving sequences.

Adult↗

Disinhibition of hippocampal pyramidal cells during the transition into theta rhythm.

The activity of hippocampal complex-spike cells (presumed pyramidal cells) and theta cells (presumed interneurons) was examined during transitions from non-theta electroencephalogram (EEG) states to theta EEG states in freely moving and sleeping rats. Theta cell firing rates were significantly depressed in a 1-s period centered on the EEG transition relative to the surrounding 1-s periods (normalized rates +/- SEM): 1.05 +/- 0.02 for the "non-theta" period, 0.59 +/- 0.03 for the "transition" period, and 1.36 +/- 0.04 for the "theta" period (n = 26 cells). Conversely, complex-spike cell firing was significantly increased during the transition period: 0.51 +/- 0.11 for the "non-theta" period, 2.24 +/- 0.19 for the "transition" period, and 0.24 +/- 0.04 for the "theta" period (n = 27 cells). This diametrically altered activity indicates that theta cells must be actively inhibited during the transition. The increased activity in complex-spike cells during the transition may be simply a release from inhibitory control by interneurons. The pattern of theta cell inhibition together with increased complex-spike cell activity appears to be a general property of transitions into the theta EEG state, irrespective of behavior. It is suggested that increased activity in septal afferents (GA-BAergic cell activity greater than cholinergic cell activity) initially inhibits hippocampal interneurons. The inhibition is not sustained because of an activity-dependent decrease in the potency of the septointerneuronal inhibition, leaving the rhythmic excitatory (cholinergic) septointerneuronal inputs, together with principal cell inputs, to increase interneuron firing rates.

Animals↗

Intermediate filament structure and assembly.

Intermediate filaments are constructed from two-chain alpha-helical coiled-coil molecules arranged on an imperfect helical lattice. Filament structure and assembly can be influenced at several different structural levels, including molecular structure, oligomer formation and filament nucleation and elongation. Consequently, it can sometimes be difficult to interpret mutagenesis data unequivocally, although regions near the amino and carboxyl termini of the rod domain of the molecule are known to be important for the production of native filaments. Imperfections in molecular packing may be important in filament assembly and dynamics.

Animals↗

The prognostic value of early CA125 serum assay in epithelial ovarian carcinoma.

We examined the prognostic value of early serum CA125 assay in 58 patients with advanced epithelial ovarian cancer together with residual disease, age, tumour grade, performance status, and the presence of ascites or adhesions at primary surgery. CA125 was a highly significant predictor of both progression free and overall survival after the first cycle and throughout primary chemotherapy. After the first cycle, CA125 was by far the most significant predictor of progression free survival (P < 0.0005). At this time, CA125 was a highly significant predictor of survival (P < 0.005), but did not add to performance status (P < 0.001) in multivariate analysis. We were able to identify three statistically-distinct prognostic groups. Patients in the upper quartile, with CA125 levels greater than 450 U ml-1, had a very poor median survival of 7 months. Patients in the lower quartile, with CA125 levels less than 55 U ml-1 had a good median survival of 23 months. Those in the two interquartile groups, who had CA125 levels ranging from 58-221 U ml-1 and 228-434 U ml-1, had relatively intermediate median survival times of 16 months and 15 months respectively. Although CA125 levels provided significant prognostic information, in the majority of patients CA125 merely confirmed overall clinical impression.

Adult↗

Factors affecting laterality of standard threshold shift in occupational hearing conservation programs.

Although noise-induced hearing loss is generally characterized as bilaterally symmetrical, 80% of audiometric shifts meeting Occupational Safety and Health Administration (OSHA) criteria were unilateral in a large industrial sample. The primary factor related to unilateral OSHA shifts was asymmetric baseline hearing level. Better ears at baseline audiogram were more likely to demonstrate OSHA shifts than poorer ears. When hearing levels were symmetric at baseline, left ears were more likely to demonstrate OSHA shifts. Although OSHA shifts were primarily unilateral, cumulative effects of noise exposure were judged to be bilaterally symmetrical due to larger hearing shifts occurring in better ears of subjects with preexisting hearing asymmetries. Recovery from temporary threshold shift in second ears tested was judged not to be a significant determinant for high prevalence of unilateral shifts. Many factors likely interact to confound interpretive value of OSHA shift laterality in occupationally noise-exposed populations. This holds important implications for hearing conservation program professionals considering hearing shift laterality as a factor in shift etiology.

Adult↗

Half-strength citrate CPD combined with a new additive solution for improved storage of red blood cells suitable for clinical use.

Currently used systems for red blood cell (RBC) collection and storage for transfusion have the disadvantage that the RBC 2,3-bisphosphoglycerate (BPG) concentration is depleted within two weeks of storage, resulting in a left-shift of the oxygen dissociation curve and a temporarily impaired capacity to deliver oxygen. We have studied the effects on red cell metabolism, morphology and in vivo recovery of 49-day storage of RBC, with collection in half-strength citrate CPD (0.5CPD) and storage in an additive solution containing citrate, adenine, mannitol, phosphate and glucose (RAS2). Traditional CPD-SAGM was used for comparison. Component preparation was performed after an initial holding period of the whole blood at ambient temperature for 8 h. The BPG concentration in 0.5CPD-RAS2 RBC was 0.633 +/- 0.120 mol (mol Hb)-1 as compared to 0.454 +/- 0.138 mol (mol Hb)-1 in CPD-SAGM RBC which implied a decrease to 67 and 48% of normal concentration, respectively. The mean RBC BPG concentration was maintained at the initial level for 28 days in the new system but decreased to very low levels within 14 days in the controls. The total adenine nucleotides were well maintained in both systems, adenosine triphosphate slightly better in the new system. Hemolysis after 49 days was 0.35 +/- 0.21% in the new system and 0.72 +/- 0.25% in the controls (p < 0.001). The morphology was better maintained in the new system (p < 0.001). The 24-hour posttransfusion survival of 49-day stored RBC was 78.9 +/- 7.1%. The membrane leakage of sodium and potassium was not significantly different in the two systems.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3-Diphosphoglycerate↗

Intrinsic properties and evoked responses of guinea pig subicular neurons in vitro.

1. Intracellular recordings were used to examine the membrane properties and evoked responses of subicular neurons in horizontal and parasagittal slices from guinea pig brain as a step toward understanding excitatory transmission through the hippocampus. 2. Most cells (49/74) could fire a burst discharge, a portion of which was Ca2+ dependent, in response to direct depolarization or in response to orthodromic or antidromic activation. Other cells (23/74) could not be made to burst, but instead fired single repetitive spikes when directly depolarized or single spikes in response to orthodromic or antidromic activation. Two recorded cells appeared to be interneurons and differed from bursting and non-bursting cells in action-potential shape and response to extracellular stimulation. 3. Bursting cells differed from nonbursting cells in their membrane properties: 1) their time constants were typically shorter (averaging 7.4 ms for bursting cells and 11.5 ms for nonbursting cells), 2) they exhibited a pronounced "sag" in the potential response to hyperpolarizing current injection, and 3) they responded at the break of a hyperpolarizing stimulus with a depolarization (anodal break potential). The sag and the anodal break potential were not detected in recordings from nonbursting neurons. 4. A single-spiking mode could be induced in bursting cells by depolarization from resting potential to about -60 mV. Conversely, hyperpolarization of nonbursting cells did not convert them to bursting cells. 5. Both bursting and nonbursting cell types could be antidromically driven. Whereas both excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs) were prominent in nonbursting cells, IPSPs were observed at a lower stimulus intensities than EPSPs in most cells. EPSPs were evident in bursting cells and they triggered burst discharges. IPSPs in bursting cells were detected only when these cells were depolarized, eliminating burst responses. 6. Spontaneous firing rates were low (averaging < 1 spike/s) for both cell types. Addition of picrotoxin produced spontaneous burst or EPSP responses in bursting cells, synchronous with different patterns of picrotoxin-induced population bursts originating in CA3 and/or entorhinal cortex. Individual subicular cells followed CA3 or entorhinal cortex or both. No such activity was recorded in nonbursting cells. No increases in activity in either cell type were seen after picrotoxin application to isolated pieces of subicular cortex.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Harvesting bone marrow in an outpatient setting using newer anesthetic agents.

PURPOSE: To evaluate the results of outpatient bone marrow harvest (BMH). PATIENTS AND METHODS: Seventy-two adult patients with various malignancies had 79 BMH procedures performed for future autologous bone marrow transplantation (BMT) in our institution's outpatient surgical facility. All patients were evaluated and educated before the procedure. Newer anesthetic agents specifically developed to have shorter half-lives, more rapid recovery from general anesthesia, and fewer unpleasant side effects were chosen. Propofol was used for induction of anesthesia in 76 patients, the other three were induced with sodium pentothal. The blood volume removed was replaced by colloid (6% hydroxyethyl starch). Also, a new parenteral nonnarcotic pain medication, ketoroloc, was used during the last part of general anesthesia to help with expected postoperative pain in 76 patients. RESULTS: BMH took 111 +/- 24 minutes and patients were in postanesthesia care unit (PACU) for 220 +/- 72 minutes before being sent home with a companion and Tylenol with codeine (acetaminophen with codeine; McNeil Pharmaceutical, Spring House, PA). PACU complications were minor and included transient mild dizziness (7.6%), vomiting (3.8%), and fever (2.6%). No life-threatening complication was observed. Only one patient was hospitalized for observation (fever) and then sent home. Seventy-five patients (94.9%) were contacted at home by the hospital nursing staff the day following the procedure. Five (6.7%) complained of nausea or vomiting, and four (5.3%) developed fever at home (temperature, 37.2 to 38.3 degrees C). Only 36% of patients actually took oral narcotic pain medication at home. CONCLUSION: Autologous BMH (AuBMH) is a safe outpatient procedure with minimal side effects when newer anesthetic agents are used.

Adolescent↗

The relaxed crossbridge pattern in isolated rabbit psoas muscle thick filaments.

Rabbit muscle is a major source of material for biochemical experiments and spin labelling studies of contraction, and so it is important to establish how closely this material resembles the frog and fish muscles usually used for structural studies. Previous studies have shown that relaxed rabbit muscle thick filaments lose the characteristic order of their crossbridges when they are cooled below about 15-19 degrees C, whereas the order of fish and frog muscles is retained above 0 degrees C. The lack of order has frustrated attempts to examine rabbit thick filament structure and has raised questions about how closely they might resemble other thick filaments. We have therefore developed a procedure for preserving the crossbridge order in isolated filaments. Electron microscopy of these thick filaments after either negative staining or metal shadowing has shown that the crossbridge pattern has a 43 nm axial repeat and is based on three near-helical strands. Computed transforms of either type of image show a series of layer lines confirming that the native relaxed pattern has been preserved, and computer reconstructions show the individual crossbridges lying on a slightly perturbed 3-stranded lattice. These data indicate an unexpectedly high degree of similarity between the rabbit and frog patterns and indicate that, in fully preserved material, there is little structural difference between the two thick filaments at the temperature at which each normally functions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗