Biomedical subjects

D Gordon

Publications and source records attributed to D Gordon.

At least 145 records · Page 8Linked to original sources

PubMed1998

A diagnostic in vitro urine assay for interstitial cystitis.

OBJECTIVES: A low molecular weight urine factor that inhibits the proliferation of normal bladder epithelial cells in vitro was previously shown to be present significantly more often in the urine of patients with interstitial cystitis (IC) than in the urine of asymptomatic age-, race-, and sex-matched control subjects. We sought to determine the specificity of this finding for IC by determining whether the urine of patients with other urogenital inflammatory disorders also contains a factor that inhibits bladder epithelial cell proliferation. METHODS: Urine was collected from women with IC, acute bacterial cystitis, or vulvovaginitis, as well as from asymptomatic control women. The proliferation of primary normal adult bladder epithelial cells was determined by measuring 3H-thymidine incorporation in vitro. RESULTS: Osmolality- and pH-corrected urine specimens from 50 (86%) of 58 women with IC significantly inhibited human bladder epithelial cell proliferation compared with 3 (8%) of 36 asymptomatic control women, 7 (12%) of 58 women with bacterial cystitis, and 0 (0%) of 12 women with vulvovaginitis (P < 0.001 for the comparison of mean percent change in 3H-thymidine incorporation with IC urine versus urine from each of the control groups). Optimal sensitivity and specificity values of 91.4% and 90.6%, respectively, were achievable at a cutoff of 25% inhibition of 3H-thymidine incorporation, using all three control groups. CONCLUSIONS: The measurement of urine antiproliferative activity may be a useful noninvasive means for diagnosing IC in women.

Adult↗

PubMed1998

Iron uptake by ferritin: NMR relaxometry studies at low iron loads.

Twenty ferritin samples were prepared at pH 6.5 with average loadings of 0-89 Fe atoms per molecule. Nuclear magnetic relaxation times T1 and T2 were measured at 3 degrees C, 23 degrees C, and at 37 degrees C and at field strength from 0.025 to 1.5 T. The field dependence, temperature dependence, and approximate equality of T1 and T2 at low fields all suggest that nuclear magnetic relaxation in this range is caused primarily by solitary Fe3+ ions. The relaxivity (relaxation rate per mM ferritin) increases quickly with initial iron loading, reaches a peak at 13-14 Fe atoms per molecule, and then declines. This provides supportive evidence for the formation of antiferromagnetically-coupled clusters during early stages in iron loading; the failure to see a similar peak in an earlier study may be related to the nonphysiological pH that was used. Above 50 atoms per molecule, the relaxivity remains approximately constant, except that 1/T2 at high fields increases slightly, consistent with early core growth. The residual ionic relaxivity in this region is consistent with about three solitary Fe3+ ions remaining on the protein shell, indicating that spin cancellation is not complete. A similar value is obtained by extrapolating relaxation data at high loadings (up to 3000 Fe atoms per molecule), suggesting that these uncoupled spins persist on the protein shell even after an appreciable core has been built.

Animals↗

PubMed1998

Depolarization differentially affects allosteric modulation by neurotoxins of scorpion alpha-toxin binding on voltage-gated sodium channels.

Voltage-gated sodium channels serve as a target for many neurotoxins that bind to several distinct, allosterically interacting receptor sites. We examined the effect of membrane potentials (incited by increasing external K+ concentrations) on the binding modulation by veratridine, brevetoxin, and tetrodotoxin of the scorpion alpha-toxin AaH II to receptor site 3 on sodium channels of rat brain synaptosomes. Depolarization is shown to differentially modulate neurotoxin effects on AaH II binding: Veratridine increase is potentiated, brevetoxin's inhibitory effect is reduced, and tetrodotoxin enhancement is evident mainly at resting membrane potential (5 mM K+). Both tetrodotoxin and veratridine apparently reverse the inhibition of AaH II binding by brevetoxin at resting membrane potential, but only veratridine is able to partially restore AaH II binding at 0 mV (135 mM K+). Thus, the allosteric interactions are grouped into two categories, depending on the membrane potential. Under depolarized conditions, the cooperative effects among veratridine and brevetoxin on AaH II binding fit the previously described two-state conformational model. At resting membrane potential, additional interactions are revealed, which may be explained by assuming that toxin binding induces conformational changes on the channel structure, in addition to being state-dependent. Our results provide a new insight into neurotoxin action and the complex dynamic changes underlying allosteric coupling of neurotoxin receptor sites, which may be related to channel gating.

Allosteric Regulation↗

PubMed1998

Consed: a graphical tool for sequence finishing.

Sequencing of large clones or small genomes is generally done by the shotgun approach (Anderson et al. 1982). This has two phases: (1) a shotgun phase in which a number of reads are generated from random subclones and assembled into contigs, followed by (2) a directed, or finishing phase in which the assembly is inspected for correctness and for various kinds of data anomalies (such as contaminant reads, unremoved vector sequence, and chimeric or deleted reads), additional data are collected to close gaps and resolve low quality regions, and editing is performed to correct assembly or base-calling errors. Finishing is currently a bottleneck in large-scale sequencing efforts, and throughput gains will depend both on reducing the need for human intervention and making it as efficient as possible. We have developed a finishing tool, consed, which attempts to implement these principles. A distinguishing feature relative to other programs is the use of error probabilities from our programs phred and phrap as an objective criterion to guide the entire finishing process. More information is available at http:// www.genome.washington.edu/consed/consed. html.

Base Sequence↗

PubMed1998

Double-blind, placebo-controlled study of magnesium hydroxide for treatment of sensory urgency and detrusor instability: preliminary results.

In a prospective, randomised, double-blind, placebo-controlled study 40 women with sensory urgency or detrusor instability randomly received either magnesium hydroxide (group A) or placebo (group B). Pre- and post-treatment symptoms, frequency-volume charts and cystometry results were compared. Eleven of 20 patients receiving magnesium (55%) reported a subjective improvement of their urinary symptoms, compared with five patients taking placebo (20%). In both study groups there was no statistically significant difference in pre- and post-treatment urodynamic parameters in those reporting symptomatic improvement. Magnesium was well tolerated by patients in group A, and no side effects were reported. These results suggest that magnesium hydroxide may be beneficial for detrusor instability or sensory urgency in women.

Dose-Response Relationship, Drug↗

PubMed1998

Brain natriuretic peptide: identification of a second natriuretic peptide in human aqueous humour.

AIMS/BACKGROUND: To measure aqueous humour levels of brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) in humans. To compare peptide levels in glaucomatous and control eyes to test the hypothesis that these peptides are increased in glaucoma. BNP and ANP are cyclic endopeptides whose principal biological effects are natriuresis and vasodilatation. Experimental glaucoma in animal models results in elevated aqueous ANP. Intravenous ANP administration in both animals and humans causes lowering of intraocular pressure (IOP). There are equivocal data to support a role for ANP in IOP regulation in human eyes. There are as yet no published data on BNP in human aqueous humour. METHOD: This was a case-control study. Cases were primary open angle, pseudoexfoliation, and mixed mechanism glaucoma eyes undergoing trabeculectomy. Controls were cataract extraction eyes. There were 47 trabeculectomy eyes (44 patients) and 47 cataract extraction eyes (46 patients) matched for age, sex, race, systemic medications, and type of anaesthetic. 100-200 microliters of aqueous humour were aspirated by paracentesis as the first step in the surgical procedure. Peptide levels were later measured by radioimmunoassay. RESULTS: The presence of BNP and ANP in human aqueous humour was confirmed. BNP was present in higher concentrations than ANP. BNP levels tended to be greater in control eyes--glaucoma median 56.5 (range 0-3526.5) pg/ml versus control median 65.16 (range 0-1788) pg/ml (Wilcoxon signed rank test p = 0.78). ANP levels tended to be greater in glaucoma eyes than in controls: glaucoma median 3 (range 0-68.5) pg/ml versus control median 0 (range 0-60) pg/ml (Wilcoxon signed rank test p = 0.82). ANP and BNP were log linearly related in both groups (r glaucoma group = 0.961, r control group = 0.894). CONCLUSION: This is the first report of BNP and ANP in human aqueous humour. Peptide levels did not differ significantly between glaucoma and cataract extraction eyes. A linear relation between log BNP and ANP was found. Further studies are required to clarify the role of these peptides in aqueous humour production and IOP regulation.

Adult↗

PubMed1998

A strategic information system to facilitate the use of performance indicators in hospitals.

Hospital management teams receive voluminous data from a wide variety of sources, but are unable to distill the essential data they require to make good decisions. We have used a methodology which helps teams define and use important management data coupled with an information system that makes this data accessible. Results of our evaluation indicate that the process of developing a balanced scorecard (BSC) indicator system helps management teams to define meaningful strategic objectives and measurable performance indicators. The framework combined with the information acts as an integrating force, providing a shared understanding of the unit's goals. We conclude that a customized decision support system which integrates multiple measures in a BSC framework is a powerful tool for enabling complex decision making by a management team.

Canada↗

PubMed1998

Hospital management decision support: a balanced scorecard approach.

Hospital management teams receive voluminous data from a wide variety of sources, but are unable to distill the essential data they require to make good decisions. We have used a methodology, which helps teams define and use important management data coupled with an information system that makes this data accessible. Results of our evaluation indicate that the process of developing a Balanced Scorecard indicator system helps management teams to define meaningful strategic objectives and measurable performance indicators. The framework combined with the information acts as an integrating force, providing a shared understanding of the unit's goals. We conclude that a customized decision support system, which integrates multiple measures in a balanced Scorecard framework, is a powerful tool for enabling complex decision making by a management team.

Cardiovascular Diseases↗

PubMed1998

Successful treatment of advanced interstitial pregnancy with methotrexate and hysteroscopy. A case report.

BACKGROUND: Data concerning medical treatment of interstitial ectopic pregnancies are scarce. These pregnancies are characterized by late and serious clinical manifestations. We report a case of advanced interstitial pregnancy treated successfully by combining methotrexate (MTX) and hysteroscopy. CASE: A routine ultrasonic evaluation of a 10-week pregnancy revealed a right interstitial gestational sac 58 mm in diameter and containing an embryo with a crownrump length of 29 mm and embryonic heartbeats. Serum beta-human chorionic gonadatropin (hCG) level was 97,950 mIU/mL. The patient was treated with a systemic MTX/leucovorin regimen. At the end of the one-week course, no embryonic cardiac activity was detected, and a decrease in beta-hCG levels commenced. Persistent trophoblastic tissue, manifested by a low (26 mIU/mL) beta-hCG level in plateau, was successfully removed by way of hysteroscopy. CONCLUSION: Early detection of interstitial pregnancy may facilitate conservative medical treatment.

Abortifacient Agents, Nonsteroidal↗

PubMed1998

Acute otitis media: the evolution of surgical management.

OBJECTIVE: Acute suppurative otitis media has been a common disease since time immemorial and, until the late nineteenth century, was followed by a high complication rate, major morbidity, and frequent mortality. Since then, the overall incidence of the disease has changed little; however, in less than a century, progressively more sophisticated surgery and the introduction of antimicrobials have reduced the mortality, at least in developed countries, to a rarity. Complications such as chronic perforation of the tympanic membrane or cholesteatoma, although much less frequent than in the past, are not uncommon. The evolution of mastoid surgery into the antibiotic era is reviewed. CONCLUSION: There is concern that with the increasing frequency of bacterial resistance to antibiotics and the decreasing familiarity of family practitioners with the clinical presentation of complicated otitis media that we may be faced with a resurgence of mastoid disease.

Acute Disease↗

PubMed1998

What is an electronic patient record?

While organizations develop their Electronic Patient Records, there will be a transition period during which computerized and paper records will both exist, possibly on multiple clinical information systems. This paper describes a model that defines the patient system of record and its constituent paper elements and electronic components. The model has been adopted by a large academic health science center for their development of an electronic patient record. The model has clarified which systems and data constitute the patient system of record and the standards and policies that apply to these systems.

Academic Medical Centers↗

PubMed1997

Gene transfer of Fas ligand induces tumor regression in vivo.

The Fas-Fas ligand (FasL) system plays an important role in the induction of lymphoid apoptosis and has been implicated in the suppression of immune responses. Herein, we report that gene transfer of FasL inhibits tumor cell growth in vivo. Although such inhibition is expected in Fas+ tumor cell lines, marked regression was unexpectedly observed after FasL gene transfer into the CT26 colon carcinoma that does not express Fas. Infection by an adenoviral vector encoding FasL rapidly eliminated tumor masses in the Fas+ Renca tumor by inducing cell death, whereas the elimination of Fas- CT26 cells was mediated by inflammatory cells. Analysis of human malignancies revealed Fas, but not FasL, expression in a majority of tumors and susceptibility to FasL in most Fas+ cell lines. These findings suggest that gene transfer of FasL generates apoptotic responses and induces potent inflammatory reactions that can be used to induce the regression of malignancies.

Adenoviridae↗

PubMed1997

Identification of structural elements of a scorpion alpha-neurotoxin important for receptor site recognition.

alpha-Neurotoxins from scorpion venoms constitute the most studied group of modifiers of the voltage-sensitive sodium channels, and yet, their toxic site has not been characterized. We used an efficient bacterial expression system for modifying specific amino acid residues of the highly insecticidal alpha-neurotoxin LqhalphaIT from the scorpion Leiurus quinquestriatus hebraeus. Toxin variants modified at tight turns, the C-terminal region, and other structurally related regions were subjected to neuropharmacological and structural analyses. This approach highlighted both aromatic (Tyr10 and Phe17) and positively charged (Lys8, Arg18, Lys62, and Arg64) residues that (i) may interact directly with putative recognition points at the receptor site on the sodium channel; (ii) are important for the spatial arrangement of the toxin polypeptide; and (iii) contribute to the formation of an electrostatic potential that may be involved in biorecognition of the receptor site. The latter was supported by a suppressor mutation (E15A) that restored a detrimental effect caused by a K8D substitution. The feasibility of producing anti-insect scorpion neurotoxins with augmented toxicity was demonstrated by the substitution of the C-terminal arginine with histidine. Altogether, the present study provides for the first time an insight into the putative toxic surface of a scorpion neurotoxin affecting sodium channel gating.

Amino Acid Sequence↗

PubMed1997

Induction of angiogenesis by lidocaine and basic fibroblast growth factor: a model for in vivo retroviral-mediated gene therapy.

A strategy of direct, in vivo retroviral-mediated gene therapy targeting capillary endothelial cells must provide an environment of active angiogenesis. Both lidocaine and basic fibroblast growth factor (bFGF) promote angiogenesis, but the angiogenic response invoked by these substances in normal skeletal muscle has not been fully characterized. We sought to characterize these agents' angiogenic effects in anterior tibialis muscles of male Sprague-Dawley rats. An injection of either 1% lidocaine with 1:100,000 epinephrine or alternate-day injections of bFGF (0.025 or 0.25 microgram) with or without heparin were tested (n = 6 muscles/condition). Rats were sacrificed 4, 7, 10, or 12 days later and muscles were evaluated histologically to determine the number of proliferating cells using 5-bromo-2'-deoxycytidine (BrdC) and evaluated for capillary density using Griffonia simplicifolia I (GSI) lectin. At all time points, lidocaine produced at least 20-fold greater capillary density and cellular proliferation than PBS control (P < 0.0001). Injections of high-dosage bFGF produced more than fivefold greater capillary density than control injections at 7 and 10 days (P < 0.001), and more than twofold greater proliferation at 4, 7, and 12 days (P < 0.001). Capillary density returned to control levels 12 days following bFGF administration, whereas it remained well above control levels for 12 days after lidocaine administration. To confirm that lidocaine can be utilized in gene therapy strategies targeting vascular endothelium and skeletal muscle fibers, concentrated pLJ retrovirus containing cDNA for the heat-stable human placental alkaline phosphatase (hpAP) marker gene was infused into the rat hindlimb vasculature 4 days post-lidocaine administration. Rats receiving pLJhpAP retrovirus demonstrated significant hpAP transgene expression in endothelial cells and myocytes 21 days after the lidocaine injection (n = 6 muscles). In contrast, controls receiving pLJhpAP infusion without prior lidocaine administration failed to demonstrate any hpAP transgene expression. Lidocaine treatment evokes a substantially higher proliferative response than bFGF and, importantly, a durable angiogenic response in skeletal muscle. Thus, lidocaine is an ideal agent to induce angiogenesis in preparation for direct in vivo retroviral-mediated gene therapy targeting vascular endothelium.

Alkaline Phosphatase↗

PubMed1997

Association of posterior p-values of S.A.G.E. SIBPAL proportion-IBD and Haseman-Elston statistics for ACTHR112.

A common practice among researchers performing linkage studies is the use of equal allele frequencies as input when reporting p-values from computer linkage programs such as S.A.G.E. SIBPAL. Our results, using 5,000 sets from a uniform-prior distribution of allele frequencies, showed that such input may be problematic. Further, we found that the S.A.G.E. SIBPAL test for proportion of alleles shared identical by descent among concordantly affected sib pairs showed a greater percentage of significant p-values with decreasing parental genotype information (Table III), while the S.A.G.E. SIBPAL Haseman-Elston test produced significant p-values comparatively less frequently (Table IV).

Alleles↗

PubMed1997

Phase-directed therapy and cardiac xenograft survival.

Xenotransplant rejection is facilitated not only by T cell upregulation but also by endothelial activation and B cell/antibody mechanisms, which standard immunosuppression is unable to overcome and xenorejection ensues. However, therapy directed specifically at each phase of xenorejection may improve xenograft survival. To study this we used a heterotopic cardiac xenotransplant mode (Syrian hamster to Lewis rat). Controls had no immunotherapy. Xenorecipients received cyclosporine to restrict T cellular response/development or cyclophosphamide, an antiproliferative, to reduce xenoreactive clones and antibody/complement injury, or anti-TNF antibody to alter cytokine cascades and endothelial activation/inflammation. Further xenorecipients received combinations. While single modalities alone did not enhance survival, combinations appeared to be at least additive in vivo, suggesting that therapy directed at specific phases of xenorejection may prove useful.

Animals↗

PubMed1997

In vitro folding and functional analysis of an anti-insect selective scorpion depressant neurotoxin produced in Escherichia coli.

The selective toxicity of depressant scorpion neurotoxins to insects is useful in studying insect sodium channel gating and has an applied potential. In order to establish a genetic system enabling a structure-activity approach, the functional expression of such polypeptides is required. By engineering the cDNA encoding the depressant scorpion neurotoxin, LahIT2, behind the T7 promoter, large amounts of recombinant insoluble and nonactive toxin were obtained in Escherichia coli. Following denaturation and reduction, the recombinant protein, constructed with an additional N-terminal methionine residue, was subjected to renaturation. Optimal conditions for reconstitution of a functional toxin, having a dominant fold over many other possible isoforms, were established. The recombinant active toxin was purified by RP-HPLC and characterized. Toxicity (ED50) to insects, binding affinity (IC50) to an insect receptor site, and electrophysiological effect on an insect axonal preparation were found to be similar to those of the native toxin. Substitution of the C-terminal glycine by a Gly-Lys-Lys triplet did not abolish folding but affected toxicity (3.5-fold decrease) of LqhIT2. Apparently, this efficient bacterial expression system (500 micrograms HPLC-purified toxin/1 liter E. coli culture) provides the means for studying structure/ activity relationship and the molecular basis for the phylogenetic selectivity of scorpion depressant neurotoxins.

Animals↗

PubMed1997

A fractured peace: a changing pattern of violence.

Since the paramilitary cease-fire in Northern Ireland in August 1994 we have seen a change in the pattern of so called 'punishment attacks'. Shootings with low velocity handguns have been replaced by severe beatings to the extremities from multiple assailants using iron bars or similar weapons. In the 18 months prior to the cease-fire there were 177 punishment shootings, which were usually relatively minor and did not require any plastic surgical expertise. Between August 1994 and November 1996, however, there were 461 punishment beatings. These beatings result in much greater morbidity and require considerable orthopaedic and plastic surgical input. In the Northern Ireland Plastic and Maxillofacial Unit we have treated 18 patients with a mean age of 22.9 years (range 16-32 years) who have been the victims of punishment beatings. These patients sustained multiple injuries, all with severe soft tissue involvement; 70% had compound fractures. The majority of patients had multiple wounds. Four patients with compartment syndrome as a result of their injuries required fasciotomies. Soft tissue reconstruction included split skin grafting (4 patients), fasciocutaneous flaps (4 patients), adipofascial flaps (2 patients), local muscle flaps (2 patients) and free muscle transfers (2 patients). Six patients required more than one procedure for soft tissue reconstruction because of multiple injuries. Each patient had a cumulative mean time in theatre of 6.7 hours. The mean hospital stay was 22.2 days (range 2-52 days). This change in the pattern of injury has led to an increased use of plastic surgical resources. Patient morbidity is significantly greater than when guns are used, and permanent disability is often the result.

Adolescent↗