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Biomedical subjects

R C Duncan

Publications and source records attributed to R C Duncan.

At least 19 recordsLinked to original sources
PubMed2000

Urinary hyaluronic acid and hyaluronidase: markers for bladder cancer detection and evaluation of grade.

PURPOSE: Specific patterns of progression and frequent recurrence of bladder tumors determine the choice of treatment, frequency of surveillance, quality of life, and ultimately, patient prognosis. The prognosis would be improved if an accurate noninvasive test was available for diagnosis. Identification of markers that function in bladder cancer progression would be helpful in designing such diagnostic tests. The glycosaminoglycan, hyaluronic acid (HA), promotes tumor metastasis. Hyaluronidase (HAase), an endoglycosidase, degrades HA into small fragments that promote angiogenesis. We have previously shown that both HA and HAase are associated with bladder cancer and may function in bladder tumor angiogenesis. In this study we examined whether urinary HA and HAase levels serve as bladder cancer markers. MATERIALS AND METHODS: Among the 513 urine specimens analyzed, 261 were from transitional cell carcinoma (TCC) patients, 9 from patients with non-TCC tumors, and 243 from controls (normals, patients with other genitourinary (GU) conditions or a history of bladder cancer (HxBCa)). The urinary HA and HAase levels were measured by two ELISA-like assays that utilize a biotinylated HA binding protein for detection. These levels were normalized to total urinary protein and were expressed as ng./mg. (HA test) and mU/mg. (HAase test), respectively. RESULTS: The urinary HA levels were elevated (2.5 to 6.5 fold) in bladder cancer patients (1173.7+/-173.4; n = 261) as compared with normals (246.1+/-38.5; n = 41); GU patients (306.6+/-32.2; n = 133), and patients with a HxBCa (351.1+/-49.1; n = 69) (p <0.001). The urinary HAase levels were elevated (3 to 7 fold) in G2/G3 bladder cancer patients (26.2+/-3.2) as compared with normals (4.5+/-0.9) and patients with either GU conditions (5.8+/-1.3), HxBCa (8.2+/-2.6) or G1 tumors (9.7+/-2.5) (p <0.001). The HA test showed 83.1% sensitivity, 90.1% specificity and 86.5% accuracy in detecting bladder cancer, regardless of the tumor grade. The HAase test showed 81.5% sensitivity, 83.8% specificity and 82.9% accuracy to detect G2/G3 patients. Combining the inferences of the HA and HAase tests (HA-HAase test) resulted in detection of bladder cancer, regardless of tumor grade and stage, with higher sensitivity (91.2%) and accuracy (88.3%), and comparable specificity (84.4%). CONCLUSION: Our results show that the HA-HAase urine test is a noninvasive, highly sensitive and specific method for detecting bladder cancer and evaluating its grade.

Adult↗
PubMed2000

Deferred treatment of localized prostate cancer in the elderly: the impact of the age and stage at the time of diagnosis on the treatment decision.

OBJECTIVE: To assess the clinical behaviour of clinically localized prostate cancer in elderly patients monitored until progression, and the impact of clinical variables, i.e. clinical stage, Gleason score, the dynamics of prostate specific antigen (PSA) and age, on the natural history of the disease. PATIENTS AND METHODS: Between February 1991 and January 1998, 54 patients (mean age 76.4 years, median 77 at the time of diagnosis) with clinically localized prostate cancer who elected for watchful waiting were identified. They were monitored regularly and treatment deferred until progression. Progression was defined as local stage progression (as assessed on a digital rectal examination), biochemical progression or metastasis. All patients who progressed were offered either radiation therapy or hormonal treatment. Each clinical variable was assessed by univariate and multivariate analysis to predict disease progression. The mean follow-up was 47 months. RESULTS: Of the 54 patients, 28 (52%) progressed; 10 had biochemical, 11 local and four biochemical and local progression, and three developed metastasis. All the patients who progressed elected to receive hormonal treatment. The mean time to progression was 35 months. Gleason score (</= 6 and > 6), age (</= 75 and > 75 years) and serum PSA level (</= 10 and > 10 ng/mL) were statistically significant predictors of disease progression (P = 0.04, < 0.001 and 0.02, respectively). The clinical stage at the time of diagnosis had a borderline effect on disease progression (P = 0.06). On multivariate analysis, Gleason score and PSA level were statistically significant predictors of disease progression. CONCLUSION: These results suggest that the treatment of prostate cancer should not be deferred in patients aged > 75 years with a good performance status when the biopsy has a Gleason score >/= 6 and the serum PSA level is >/= 10 ng/mL.

Age Factors↗
PubMed2000

Identification of trauma patients at risk of thoracic aortic tear by mechanism of injury.

OBJECTIVE: We sought to identify potential measurable on-scene information that would assist clinicians in the identification of patients at risk for thoracic aortic tear (AT) after vehicular trauma. METHODS: Data were prospectively collected at the scene of 295 motor vehicle crashes from 1995 to 1999. There were 34 cases (12%) with AT. Scene data consisted of vehicle maximal crush, maximal intrusion into the occupant compartment, change in velocity (Delta V) and principal direction of force. Thoracic aortic injuries were confirmed radiographically or at autopsy. Crash factors were analyzed for correlation with AT by logistic regression. RESULTS: Delta V > or = 20 mph and near-side impact were the factors having the strongest correlation with thoracic aortic injury. Delta V > or = 20 mph (n = 32 with AT) had an odds ratio = 6.4, (p < 0.01). Near impact (n = 20 with AT) had an odds ratio = 2.3, (p < 0.05) and intrusion > or = 15 inches had an odds ratio = 3.2, p < 0.05. The sensitivity, specificity, and accuracy of the presence of near impact, Delta V > or = 20 mph, or both, were 100%, 34%, and 64%. The positive and negative predictive values were 16% and 100%, respectively. There was no relationship of AT to use of seat belts or airbags. CONCLUSION: Thoracic aortic injury after vehicular collision can be reliably excluded if near-impact, Delta V > or = 20 mph, or intrusion > or = 15 inches are not present. Mechanism of injury in the form of crash scene information may aid clinicians in identifying individuals at risk for thoracic aortic tear after vehicular trauma.

Accidents, Traffic↗
PubMed2000

MR imaging and localized proton spectroscopy of the precentral gyrus in amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: In the search for a diagnostic test for amyotrophic lateral sclerosis (ALS), especially upper motor neuron (UMN) involvement, MR imaging and proton spectroscopy techniques have each received attention, but their findings have not been correlated. The purpose of this study was to identify relationships among the results of current techniques, taking into account the severity of clinical UMN disease, so that objective measures of the pathogenesis of ALS may be established. METHODS: Eighteen subjects with clinically diagnosed ALS and 12 healthy volunteers underwent MR imaging of the brain and localized proton MR spectroscopy. Water-suppressed spectra from the left precentral gyrus and from the left cuneus gyrus were analyzed with the LCModel method, yielding concentrations for N-acetyl (NA), total creatine (Cr), choline (Cho), glutamate (Glu), glutamine (Gin), and myo-inositol (Ins) metabolic substrates. Signal intensities of the precentral gyrus on T2-weighted images were assessed qualitatively in a blinded fashion. RESULTS: For the precentral gyrus, mean Cho (1.3 mM) and Ins (3.25 mM) for the ALS group were significantly increased. After adjustment for Cr covariance, mean Glu (5.08 mM) and NA (6.31 mM) were decreased. For the cuneus gyrus, no difference in metabolite concentrations between groups was observed. Trend analysis of the precentral gyrus metabolite concentrations revealed significant increases in Cho and Ins and decreases in NA and Glu with respect to the severity of clinical UMN signs. Metabolic changes were greater in the subset of ALS patients with precentral gyrus signal changes on imaging, and significantly increased Ins was associated with cortical hypointensity on fast spin-echo images. CONCLUSION: Mean metabolite concentrations determined from precentral gyrus spectra reflect clinical and pathologic changes that occur in ALS. Imaging findings, while related to the spectral and clinical results, are not specific to ALS.

Adult↗
PubMed1999

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↗
PubMed1999

Transcranial doppler detection of fat emboli.

BACKGROUND AND PURPOSE: The fat embolism syndrome (FES) is characterized by the simultaneous occurrence of pulmonary and neurological symptoms as well as skin and mucosal petechiae in the setting of long-bone fractures or their surgical repair. Its pathophysiology is poorly understood, and effective treatments are lacking. We present 5 patients with long-bone fractures in whom in vivo microembolism was detected by transcranial Doppler. METHODS: Five patients with long-bone fractures were monitored with transcranial Doppler for microembolic signals (MESs) after trauma. Two patients also had intraoperative monitoring. A TC-2020 instrument equipped with MES detection software was used. Detected signals were saved for subsequent review. Selected signals satisfied criteria defined previously and were categorized as large or small. RESULTS: Cerebral microembolism was detected in all 5 patients and was transient, resolving within 4 days of injury. Intraoperative monitoring revealed an increase in MESs during intramedullary nail insertion. The characteristics of MESs after injury varied among patients, with large signals being more frequent in the only patient with a patent foramen ovale. CONCLUSIONS: Cerebral microembolism after long-bone fractures can be detected in vivo and monitored over time. These findings may have potential diagnostic and therapeutic implications.

Accidents, Traffic↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1997

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗