PubMed HealthSearch

Biomedical subjects

R C Duncan

Publications and source records attributed to R C Duncan.

At least 19 recordsLinked to original sources

Perceived difficulty in dealing with consequences of spinal cord injury.

OBJECTIVES: To determine the perceived difficulty in dealing with consequences of spinal cord injury (SCI) and to explore patterns of how these complications are perceived. DESIGN: Postal survey. SETTING: General community. PARTICIPANTS: Individuals with traumatic SCI (n = 430). METHODS: Subjects (n = 877) were selected from The Miami Project database and were sent a questionnaire in which they were asked to rate their difficulty in dealing with 10 consequences of SCI, on a scale ranging from 0 (not hard at all) to 10 (extremely hard). RESULTS: The questionnaire was returned by 430 individuals (49%). Five consequences (decreased ability to walk or move, decreased control of bowel, decreased control of bladder, decreased sexual function, and pain) were rated highest (means, 8.2 to 6.2). High ratings of feeling sad were associated with high ratings of most other consequences, and a cluster analysis revealed interrelationships between the ways the various consequences were perceived. CONCLUSIONS: Several consequences of SCI are frequently perceived as being very difficult to deal with. Sadness may influence how well a person deals with other consequences of SCI. The observed patterns in perceived difficulty dealing with complications of SCI need to be explored further because they are important in our understanding and treatment of the medical conditions that may follow SCI.

Adult

Does a radiation dose-response relation exist concerning survival of patients who have soft-tissue sarcomas of the extremities? Radiation dose-response relation for soft-tissue sarcomas.

This study analyzes a single-institution experience by evaluating the impact on survival of increasing total dose of adjunctive irradiation in patients who had extremity soft-tissue sarcoma (ESTS). A retrospective review of the tumor registry at a university medical center from January 1984 through December 1992 yielded a total of 59 surgical patients of ESTS. With follow-up ranging from 30 to 135 months (median, 65 months), the 2-, 5-, and 8-year overall and disease-free survival for all patients was 86%, 71%, 58% and 76%, 70%, 56%, respectively. Multivariate analyses using the Cox proportional hazards model revealed that total radiation dose (p = 0.02), American Joint Committee on Cancer stage (p = 0.04), and tumor size (p = 0.006) were all significant prognostic factors of overall survival; however, only tumor size was predictive of disease-free survival (p = 0.02). When the effect of tumor size and disease stage were controlled in the Cox model, a dose-response curve between increasing total radiation dose and improved overall patient survival was indicated. This study demonstrates the significance of tumor size on predicting both overall and disease-free survival in patients who have soft-tissue sarcomas of the extremity. It also suggests, however, that a radiation dose-response relation may exist for overall survival. Future investigations should consider evaluating the minimal total radiation dose needed to optimize patient survival after limb-sparing surgery.

Adolescent

Social anxiety and training in neurolinguistic programming.

The Liebowitz Social Phobia Scale measured the effect of training on social anxiety responses of 28 adults prior to and following a 21-day residential training, and at 6 mo. follow-up. Significant reductions posttraining and at follow-up were evident in the mean self-reported global scale scores on fear and avoidance behavior in social situations. The item scores, aggregated to reflect the situational domains of formal and informal speaking, being observed by others, and assertion, showed significant and continuing reduction from posttraining through follow-up. These findings are consistent with the hypothesis that this training may be associated with reduced responses to social anxiety, but as there was no formal control group, pretest scores from another study were used. Interpretation is limited.

Adult

La autoantigen binding to a 5' cis-element of rubella virus RNA correlates with element function in vivo.

Rubella virus genomic RNA contains a 5' stem-loop (5'(+) SL) which is required for efficient translation and replication. The La autoantigen previously was shown to bind this RNA sequence in vitro. Results reported here demonstrate that this cellular RNA-binding protein binds to the RV 5' SL RNA with sufficient specificity for the binding to occur in the presence of excess total cellular RNA. Further, the affinity of purified La for the RV sequence is similar to its affinity for known cellular substrates. To address the functional significance of La binding, mutant forms of the RV 5'(+) SL were analysed which bind La weaker or stronger than the native form. These three forms of the RV 5' SL were incorporated into RV-luciferase constructs which expressed luciferase activity in transient transfection. The level of expression from each construct correlated with the ability of its RV sequence to bind La. The detection of La/RV RNA complexes in infected cells further supported the physiological relevance of this interaction. Possible implications of autoantigen La interaction with RV RNA for rubella virus pathology and vaccine associated adverse reactions are discussed.

Animals

The far upstream element-binding proteins comprise an ancient family of single-strand DNA-binding transactivators.

The cloning and expression of two new human cDNAs encoding proteins highly related to the far upstream element-binding protein (FBP) are described. FBP, FBP2, and FBP3 comprise a family of single-strand DNA- binding proteins that possess all of the general features of more conventional transcription factors. The FBPs each bind sequence specifically to only one strand of the far upstream element (FUSE; originally identified upstream of c-myc), and each possesses potent activation domains when fused to the GAL4 DNA-binding domain and assayed by transient transfection. Typical of transcription factors, the proteins are most highly related in their central, DNA-binding domains, but extensive homology is also shared within the tyrosine-rich, carboxyl-terminal activation domains. Comparison with GenBank sequences revealed a fourth FBP family member encoded by Caenorhabditis elegans chromosome III, illustrating the high degree of homology in this evolutionarily ancient and conserved family.

Amino Acid Sequence

Isolation and characterization of Leishmania donovani calreticulin gene and its conservation of the RNA binding activity.

Calreticulin has been implicated in multiple cell functions. Recently, we have shown that both human and simian calreticulin are RNA binding proteins and that their binding activity is due to phosphorylation. To demonstrate that the RNA binding property of calreticulin is an intrinsic part of this multi-functional molecule and is evolutionarily conserved, we isolated and characterized the calreticulin gene from the unicellular parasite, Leishmania donovani. Amino acid sequence homology between human and Leishmania calreticulin (L. d. cal) is limited, but like the human homologue, L. d. cal binds Ca+2, can be phosphorylated in vitro and binds certain RNA sequences in a phosphorylation-dependent manner. Unlike human calreticulin, L. d. cal is glycosylated and its binding to endogenous Leishmania RNA is phosphorylation-independent. The binding of L. d. cal to Leishmania RNA suggests that the RNA binding activity of calreticulin has remained evolutionarily conserved.

Amino Acid Sequence

Activated platelet aggregates in thrombotic thromboctyopenic purpura: decrease with plasma infusions and normalization in remission.

Circulating activated platelet aggregates (aPA) were assayed by flow cytometry employing mAb alpha-CD62p in eight patients with thrombotic thrombocytopenic purpura (TTP). Elevation of aPA was observed in all patients in active stages of TTP; aPA normalized in remission. Plasma infusions with plasmapheresis decreased aPA in responding patients. The rise and fall of aPA preceded relapses and improvements, respectively. These changes were seen prior to the traditional indicators, LDH, haematocrit, and platelet count. Incubation of plasma from TTP patients with normal whole blood induced formation of aPA; this effect was significantly greater than that of plasmas from ITP patient controls (P < 0.01), suggesting the presence of an aPA-promoting factor in TTP plasma. Parallel experiments using a platelet aggregometer failed to detect effect of TTP plasma on normal blood. In summary, aPA appear to be a marker of disease activity, rising with relapse, falling with plasma therapy, and normalizing in remission. The flow cytometric assay of aPA is more sensitive than aggregometry in detecting the putative aPA-promoting factor in TTP.

Flow Cytometry

Multiple single-stranded cis elements are associated with activated chromatin of the human c-myc gene in vivo.

Transcription activation and repression of eukaryotic genes are associated with conformational and topological changes of the DNA and chromatin, altering the spectrum of proteins associated with an active gene. Segments of the human c-myc gene possessing non-B structure in vivo located with enzymatic and chemical probes. Sites hypertensive to cleavage with single-strand-specific S1 nuclease or the single-strand-selective agent potassium permanganate included the major promoters P1 and P2 as well as the far upstream sequence element (FUSE) and CT elements, which bind, respectively, the single-strand-specific factors FUSE-binding protein and heterogeneous nuclear ribonucleoprotein K in vitro. Active and inactive c-myc genes yielded different patterns of S1 nuclease and permanganate sensitivity, indicating alternative chromatin configurations of active and silent genes. The melting of specific cis elements of active c-myc genes in vivo suggested that transcriptionally associated torsional strain might assist strand separation and facilitate factor binding. Therefore, the interaction of FUSE-binding protein and heterogeneous nuclear ribonucleoprotein K with supercoiled DNA was studied. Remarkably, both proteins recognize their respective elements torsionally strained but not as liner duplexes. Single-strand- or supercoil-dependent gene regulatory proteins may directly link alterations in DNA conformation and topology with changes in gene expression.

Base Sequence

Platelet factor 3 in plasma fractions: its relation to microparticle size and thromboses.

Platelet factor 3 (PF3) was assayed by Russell's viper venom (RVV) in three plasma fractions, platelet-rich plasma (PRP), platelet poor plasma (PPP), and 0.1 microns particle-filtered plasma (PFP), in 42 healthy controls, 34 patients with recent cerebrovascular accidents (CVA) and 28 with recent ischemic events from coronary artery disease (CAD). Platelet microparticles (PMP) were assayed in PPP by flow cytometry. Relative to controls, the RVV clotting times were shortened in all three plasma fractions in both patient groups, p < 0.001. PMP were also elevated in both patient groups, p < 0.001. Linear regression analysis showed that the RVV times of PPP are inversely correlated with PMP, p < 0.005, in patient groups but not in controls. There was no correlation of RVV time with PT, APTT or FIB. After converting RVV times to units of PF3 activity, it could be shown that only about 1/4 of the total PF3 activity was contributed by platelets. The major contribution to the PF3 activity in controls was from microparticles < 0.1 microns but in patients was due mainly to microparticles > 0.1 microns. The RVV time was superior to routine coagulation tests in discriminating thrombotic patients from healthy controls.

Adolescent

Comparison of digitized ECGs simultaneously recorded with CR and V leads.

Evidence is presented that electrocardiograms recorded with bipolar chest-right arm (CR) leads are diagnostically similar to electrocardiograms recorded with unipolar V leads. Electrocardiograms were simultaneously recorded with CR and V leads on six chest sites in 45 cardiac patients and submitted, unmarked, for evaluation, by four cardiologists. In spite of relatively small differences in the amplitudes of P, Q, R, S, and T waveforms, the diagnosis based on tracings recorded with CR leads was similar to the diagnosis based on tracings recorded with V leads in nearly 90% of patients. Because CR leads are set up with only two electrodes, one on the right arm and one on the chest, their use in cardiac emergencies saves time and simplifies the recording technique. This investigation is part of a project aimed at developing a portable electrocardiograph for use outside the hospital or clinic.

Electrocardiography

Relation between blood pressure and outcome in intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Controversy continues to exist regarding optimal blood pressure control in acute hypertensive intracerebral hemorrhage. Persistent marked elevation of the blood pressure can promote further bleeding, increase cerebral blood flow, and raise intracranial pressure. Relative hypotension, on the other hand, may promote hypoperfusion with secondary ischemia. This study was designed to assess outcome in patient groups defined by the degree of elevation in their pretreatment and posttreatment blood pressures. METHODS: We retrospectively assessed 87 patients who were categorized according to an initial mean arterial pressure > 145 mm Hg (n = 34) compared with those with a pressure < or = 145 mm Hg (n = 53). We also studied blood pressure control within the first 2 to 6 hours of presentation with subjects categorized according to a mean arterial pressure > 125 mm Hg (n = 40) or < or = 125 mm Hg (n = 47). RESULTS: An improved outcome in both mortality and severe morbidity was observed in the < or = 145 (chi 2 = 7.0, P < .005) and the < or = 125 mm Hg (chi 2 = 6.7, P < .005) groups. CONCLUSIONS: Markedly elevated blood pressure on admission and persistent inadequate blood pressure control adversely affect the prognosis in hypertensive intracerebral hemorrhage.

Adult

Acute leukocyte and temperature response in hypertensive intracerebral hemorrhage.

BACKGROUND AND PURPOSE: We undertook this study to investigate the relationship between outcome, hematoma volume, and admission peripheral white blood cell count and body temperature in acute hypertensive intracerebral hemorrhage. METHODS: Eighty-two consecutive patients who presented with hypertensive intracerebral hemorrhage within 72 hours of onset were retrospectively assessed. The peripheral white blood cell count, polymorphonuclear leukocytes, and the body temperature on admission were measured. The outcome at 30 days after ictus was determined with a modified Glasgow Outcome Scale. Correlation analysis was performed between these measurements and hematoma volume, which was calculated by brain computed tomography. We also looked at the presence or absence of intraventricular extension. RESULTS: The mean hematoma volume was significantly greater in those patients who died compared with those with a good, moderate, and severe outcome (79.6 cm3 versus 10.7, 18.3, and 19.9 cm3, respectively; P < .0005). The mean peripheral white blood cell count was higher in those who died than in the other three groups (12.580 +/- 0.521 versus 8.160 +/- 0.543, 8.565 +/- 0.543, and 7.427 +/- 0.786 x 10(9)/L, respectively; P < .0005). The mean body temperature of those who died tended to be higher than those in the good-outcome group (99.12 +/- 0.21 versus 98.18 +/- 0.21 degrees F, P < .05). A positive linear correlation was observed between hematoma volume and white blood cell count (r = .506, df = 77, P < .001), as well as the polymorphonuclear leukocyte count (r = .561, df = 76, P < .001). A trend was also observed for admission temperature (r = .265, df = 74, P < .05). The leukocyte response was enhanced by the presence of intraventricular extension. CONCLUSIONS: There is a relationship between the size of the hematoma and the degree of leukocytosis in hypertensive intracerebral hemorrhage. This relationship appears to most likely represent a stress-induced reaction of the white blood cell count.

Aged

Using computers to diagnose and plan treatment of approximal caries. Detected in radiographs.

Two of the authors developed a computer-based software system that is capable of diagnosing approximal caries and making decisions about restorative care. The system was compared with decisions made by a group of experienced clinicians. The results indicate that the clinician viewers overall correctly identified a similar number of surfaces as the software, but from viewer to viewer, there was more variability in the number of surfaces identified correctly than in those identified correctly by the software users. Software packages such as this have the potential to raise overall accuracy by increasing the consistency of treatment decisions over time.

Bicuspid

Phase I and pharmacokinetics studies of prochlorperazine 2-h i.v. infusion as a doxorubicin-efflux blocker.

In an earlier phase I study, we reported that the maximal tolerated dose (MTD) of prochlorperazine (PCZ) given as a 15-min i.v. infusion was 75 mg/m2. The highest peak plasma PCZ concentration achieved was 1100 ng/ml. The present study was conducted to determine if PCZ levels high enough to block doxorubicin (DOX) efflux in vitro could be achieved and sustained in vivo by increasing the duration of i.v. infusion from 15 min to 2 h. The treatment schedule consisted of i.v. prehydration with at least 500 ml normal saline (NS) and administration of a fixed standard dose of 60 mg/m2 DOX as an i.v. bolus over 15 min followed by i.v. doses of 75, 105, 135, or 180 mg/m2 PCZ in 250 ml NS over 2 h. The hematologic toxicities attributable to DOX were as expected and independent of the PCZ dose. Toxicities attributable to PCZ were sedation, dryness of mouth, anxiety, akathisia, hypotension, cramps, and confusion. The MTD of PCZ was 180 mg/m2. Large interpatient variation in peak PCZ plasma levels (91-3215 ng/ml) was seen, with the plasma half-life (t1/2 alpha) being approximately 57 min in patients given 135-180 mg/m2 PCZ. The volume of distribution (Vd), total clearance (ClT), and area under the curve (AUC) were 350.1 +/- 183.8 1/m2, 260.7 +/- 142.7 l m2 h-1 and 1539 +/- 922 ng ml h-1, respectively, in patients given 180 mg/m2 PCZ and the respective values for patients receiving 135 mg/m2 were 48.9 +/- 23.76 l/m2, 33.2 +/- 2.62 l m2 h-1, and 4117 +/- 302 ng ml h-1. High PCZ plasma levels (> 600 ng/ml) were sustained in all patients treated with 135 mg/m2 PCZ for up to 24 h. DOX plasma elimination was biphasic at 135 and 180 mg/m2 PCZ, and a > 10-ng/ml DOX plasma level was maintained for 24 h. Partial responses were seen in three of six patients with malignant mesothelioma, in two of ten patients with non-small-cell lung carcinoma, and in the single patient with hepatoma. Our data show that PCZ can be safely given as a 2-h infusion at 135 mg/m2 with clinically manageable toxicities. The antitumor activity of the combination of DOX and PCZ needs to be confirmed in phase II trials.

Adult

Gold alloy cast to base metal removable partial denture frameworks.

For many years, gold and base metal alloys have been used in the construction of cast removable partial dentures. Each alloy has desirable properties, yet neither is ideally suited for all portions of a framework. A method has been developed to fabricate prostheses by casting gold alloy against a base metal alloy. This procedure allows the practitioner to combine the favorable characteristics of both alloys within a single framework. Consequently, the practitioner may create frameworks that more effectively meet the biomechanical demands of the oral environment.

Dental Alloys

A quantitative assessment of renal blood flow autoregulation in experimental diabetes.

Several approaches have been utilized to describe renal blood flow (RBF) autoregulation in normal and pathological conditions. When describing the relation between RBF and stepwise decrements in renal perfusion pressure (RPP), these methods have several limitations, including: the necessity for predetermining a pressure 'break-point', and establishing constraints on changes in flow. To circumvent these limitations, we successfully utilized a third order polynomial, the cubical parabola, to characterize the autoregulatory responses in untreated streptozotocin (STZ) diabetic and control rats. The nonlinear relationship occurring between RBF and RPP was estimated from individual observations using the equation RBF = a + b x 10(-6) (RPP-c)3. Variables a and c represent RBF and RPP at the inflection point of the curve, respectively; variable b represents the rate of fall of RBF as RPP decreases (shape factor). Variable c was significantly lower in the diabetic group than in the control group whereas variable b was greater in the diabetic group. RBF (a) did not differ between the two groups. In conclusion, we determined that the range of RBF autoregulation in untreated diabetic rats is reset to a lower RPP. Furthermore, the curve below the inflection point declines more rapidly in diabetic rats than in controls. We propose that the equation described herein constitutes a promising and reproducible method for describing RBF autoregulation in vivo.

Animals