GLP-2 cloning may lead to therapy for intestinal deficiency diseases.
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Genome, Bacterial↗
Biomedical subjects
D Gordon
Publications and source records attributed to D Gordon.
Prevalence and characteristics of voiding difficulties in women: are subjective symptoms substantiated by objective urodynamic data?
OBJECTIVES: To examine the prevalence and characteristics of voiding difficulties in women. METHODS: Two hundred six consecutive female patients who attended a urogynecology clinic were recruited. Patients were interviewed regarding the presence and severity of symptoms that would suggest voiding difficulties (ie, hesitancy, straining to void, weak or prolonged stream, intermittent stream, double voiding, incomplete emptying, reduction, and positional changes to start or complete voiding). Urodynamic evidence of voiding difficulty was considered as a peak flow rate less than 12 mL/s (voided volume greater than 100 mL), or residual urine volume greater than 150 mL, on two or more readings. Residual urinary volume, flow patterns, and pressure-flow parameters were analyzed and compared between symptomatic and asymptomatic patients who had urodynamic parameters of voiding difficulties. RESULTS: One hundred twenty-seven (61.7%) women reported having voiding difficulty symptoms; 79 others (38.3%) were free of such symptoms. Urodynamic diagnosis of voiding difficulty was made in 40 women (19.4% of the study population): 27 in the symptomatic group and 13 in the asymptomatic group (21.2% and 16.5%, respectively). Only 1 patient had voiding difficulty due to bladder outlet obstruction. All other cases of low flow rate were due to impaired detrusor contractility. CONCLUSIONS: Objective evidence of voiding difficulty may be found in both symptomatic and asymptomatic patients and is usually due to impaired detrusor contractility. The clinical significance of the abnormal flow parameters in asymptomatic patients is unclear.
Female↗
The long isoform uncoupling protein-3 (UCP3L) in human energy homeostasis.
The biological role(s) proposed for UCP3 in energy homeostasis have been based primarily upon amino acid sequence homology to UCP1. Spontaneous mutations of UCP3> have been described in humans, but not in rodents. The functional consequences-or lack thereof-of these mutations in humans will be of great importance in elucidating the biology of this protein. The results of two such studies are summarized here.
Animals↗
Association between a marker in the UCP-2/UCP-3 gene cluster and genetic susceptibility to anorexia nervosa.
Anorexia nervosa (AN) is an enigmatic syndrome affecting approximately 0.1% of the at risk population in the UK which equates to approximately 70000 sufferers. Data from a number of studies have demonstrated the heritability of this disorder, however it is only in the last few years that studies have begun to determine the involvement of particular candidate genes in this genetic predisposition. In the current study we have used classical case-control association analysis to determine whether two highly polymorphic microsatellite markers, located within a 3-cM region of the UCP-2/UCP-3 locus, show involvement of this region of the human genome in the predisposition to AN. Analysis of a cohort of 170 female Caucasian anorexia nervosa sufferers and 150 normal female controls shows evidence of association with the marker D11S911 but not D11S916. Allele 13 of the marker D11S911 is significantly over represented in the anorexia nervosa population suggesting that a mutation in linkage disequilibrium with this locus may form part of the genetic component of AN. Further work is now required to try to reproduce these data in a second independent cohort and to further characterise this region of the human genome.
Adolescent↗
Scorpion alpha-like toxins, toxic to both mammals and insects, differentially interact with receptor site 3 on voltage-gated sodium channels in mammals and insects.
alpha-Like toxins, a unique group designated among the scorpion alpha-toxin class that inhibit sodium channel inactivation, are highly toxic to mice but do not compete for alpha-toxin binding to receptor site 3 on rat brain sodium channels. We analysed the sequence of a new alpha-like toxin, which was also highly active on insects, and studied its action and binding on both mammalian and insect sodium channels. Action of the alpha-like toxin on isolated cockroach axon is similar to that of an alpha-toxin, and the radioactive toxin binds with a high affinity to insect sodium channels. Other sodium channel neurotoxins interact competitively or allosterically with the insect alpha-like toxin receptor site, similarly to alpha-toxins, suggesting that the alpha-like toxin receptor site is closely related to receptor site 3. Conversely, on rat brain sodium channels, specific binding of 125I-alpha-like toxin could not be detected, although at high concentration it inhibits sodium current inactivation on rat brain sodium channels. The difficulty in measuring binding to rat brain channels may be attributed to low-affinity binding due to the acidic properties of the alpha-like toxins that also impair the interaction with receptor site 3. The results suggest that alpha-like toxins bind to a distinct receptor site on sodium channels that is differentially related to receptor site 3 on mammalian and insect sodium channels.
Animals↗
Incidence and obstetric risk factors of postpartum anal incontinence.
BACKGROUND: Anal incontinence in young women may be the result of injury to the pelvic floor during vaginal delivery. This study was conducted to evaluate the relationship between obstetric risk factors and the prevalence of anal incontinence 3 months and 1 year after delivery. METHODS: Three hundred consecutive women who delivered in the obstetric ward of the Lis Maternity Hospital, Tel Aviv Sourasky Medical Center, were prospectively interviewed 3 months postpartum with regard to the symptom of anal incontinence. Patients with anal incontinence that started after delivery were questioned about the type, frequency, and severity of the problem, concomitant stress urinary incontinence (SUI), previous colorectal assessment, and wish for further evaluation and treatment. Obstetric data were collected from the women's medical charts. Symptomatic patients were followed-up 1 year postpartum. RESULTS: Anal incontinence was reported by 21 patients: 19 were incontinent to gas, whereas only 2 patients were incontinent to solid feces (6.3% and 0.7% of the study population, respectively). Five patients (24% of the anal-incontinent patients) also had concomitant SUI. The length of the first and second stages of labor, operative vaginal delivery, and episiotomy were found to be associated (P < 0.05) with the development of anal incontinence at 3 months postpartum. At I year postpartum all patients with combined anal incontinence and SUI had persistent symptoms. CONCLUSION: The major obstetric risk factors for postpartum anal incontinence are prolonged first and second stages of labor, operative vaginal delivery, and the use of episiotomy.
Adult↗
Evaluation of a local cooperative project to improve postoperative pain management in Wisconsin hospitals.
The effectiveness of a local collaborative quality improvement project in improving the management of postoperative pain for Wisconsin Medicare patients was assessed. Six quality indicators were evaluated on the basis of baseline data from 714 subjects at 15 collaborating hospitals and follow-up data from 406 subjects from the same 15 hospitals. After efforts to improve postoperative pain management, there was statistically significant improvement in all six quality indicators.
Aged↗
Timing of sonohysterography in menstruating women.
A prospective, blind study was carried out on 44 patients to evaluate the most suitable time to perform transvaginal sonohysterography. On the day of arrival at our unit, regardless of their cycle day, the women underwent sonohysterographic evaluation, which was repeated during the first 10 days of the next cycle. Patients with sonohysterographic findings underwent hysteroscopy. According to the timing of the first examination, they were divided into two groups, i.e. group 1 for the first 10 days of the cycle, and group 2 for days 16 through 28. At the end of the study the groups were compared. The results showed a false-positive rate of 27% in group 2, while no false-positive was found in group 1. We concluded that the best time for sonohysterography in patients who still have their menstrual period is during the first 10 days of the cycle.
Adult↗
True pedigree errors more frequent than apparent errors for single nucleotide polymorphisms.
Single nucleotide polymorphisms (SNPs) are currently being developed for use in disequilibrium analyses. These SNPs consist of two alleles with varying degrees of polymorphism. A natural design for use with SNPs is the 'haplotype relative risk' sampling design in which a father, mother, and child are typed at an SNP locus. Given such a trio of genotypes, we ask: what is the probability that a pedigree error (a change from one allele to the other) at an SNP locus will be detected using only Mendel's laws as a check? We calculate the probability of detecting such errors for a hypothetical SNP locus with varying degrees of polymorphism and for various true error rates. For the sets of allele frequencies considered, we find that the detection rates range between 25 and 30%, the detection rate being lowest when the two alleles have equal frequencies and the highest when one allele has a frequency of 10%. Based on this detection rate, we determine that the true error rate is roughly 3.3-4 times that of the apparent error rate at an SNP locus. The greatest discrepancy between true and apparent error rates occurs when allele frequencies are equal.
Alleles↗
Genetic and physiologic analysis of the role of uncoupling protein 3 in human energy homeostasis.
By virtue of its potential effects on rates of energy expenditure, uncoupling protein 3 (UCP3) is an obesity candidate gene. We identified nine sequence variants in UCP3, including Val9Met, Val102Ile, Arg282Cys, and a splice site mutation in the intron between exons 6 and 7. The splice mutation results in an inability to synthesize mRNA for the long isoform (UCP3L) of UCP3. Linkage (sib pair), association, and transmission disequilibrium testing studies on 942 African-Americans did not suggest a significant effect of UCP3 on body composition in this group. In vastus lateralis skeletal muscle of individuals homozygous for the splice mutation, no UCP3L mRNA was detectable; the short isoform (UCP3S) was present in an increased amount. In this muscle, we detected no alterations of in vitro mitochondrial coupling activity, mitochondrial respiratory enzyme activity, or systemic oxygen consumption or respiratory quotient at rest or during exercise. These genetic and physiologic data suggest the following possibilities: UCP3S has uncoupling capabilities equivalent to UCP3L; other UCPs may compensate for a deficiency of bioactive UCP3L; UCP3L does not function primarily as a mitochondrial uncoupling protein.
Alternative Splicing↗
Bilateral pleural effusions in a beta-thalassemia intermedia patient with posterior mediastinal extramedullary hematopoietic masses.
Intractable bilateral exudative pleural effusions developed, following systemic sepsis without pulmonary infection, in a beta-thalassemia intermedia patient with longstanding mediastinal hematopoietic masses. The pleura were not infiltrated by hematopoietic cells. Bilateral talc pleurodesis successfully controlled the effusions.
Adult↗
Redefining processes to create a more humane patient environment.
With all that is happening in health care, too many hospital administrators forget that the organization is not guaranteed long-term success just because illness will never become extinct. David Gordon, Ph.D., writes that hospitals must satisfy patients by improving processes that ensure the hospital's long-term viability.
Hospital Administration↗
Plastic innovations: background material for microvascular anastomosis.
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Anastomosis, Surgical↗
Merging multiple institutions: information architecture problems and solutions.
Amalgamating organizations face great challenges when trying to merge their formerly separate information systems. An architectural approach is essential in order to understand the business process and data implications of the new organization's business decisions and application choices. HL7 is useful as a common messaging standard, but does not help to reconcile conflicting local identifier coding systems. The Information Services department has an important role in catalyzing decisions about inconsistent business processes and conflicting universal coding systems within an enterprise framework.
Computer Systems↗
Strategic management of an electronic patient record project using the balanced scorecard.
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Humans↗
Helicobacter pylori products upregulate neutrophil superoxide anion production.
Helicobacter pylori-neutrophil interactions may play a pathogenic role in H. pylori-induced gastritis and peptic ulcer disease. To understand these interactions, we explored the effects of H. pylori-derived products on neutrophil chemotaxis and superoxide anion production. H. pylori bacteria were cultured and supernatants fractionated. Neutrophil chemotactic activity was confirmed in the crude supernatants and in one fractionated peak corresponding to a previously described neutrophil chemotactic factor. H. pylori-derived crude supernatant, sonicate and all chromatography-derived peaks failed to directly stimulate neutrophil superoxide anion production. However, after pretreatment with sonicate, neutrophils demonstrated increased superoxide anion production (priming) following subsequent exposure to the secretagogue fmet-leu-phe. These results suggest that H. pylori products may attract neutrophils to the gastric mucosa without initially stimulating superoxide anion production or tissue injury. Oxygen radical-mediated gastric mucosal injury may subsequently result when these primed neutrophils undergo additional stimulation by as yet unidentified factors.
Chemotaxis, Leukocyte↗
Delta-atracotoxins from Australian funnel-web spiders compete with scorpion alpha-toxin binding on both rat brain and insect sodium channels.
Atracotoxins are novel peptide toxins from the venom of Australian funnel-web spiders that slow sodium current inactivation in a similar manner to scorpion alpha-toxins. To analyse their interaction with known sodium channel neurotoxin receptor sites we determined their effect on scorpion toxin, batrachotoxin and saxitoxin binding. Nanomolar concentrations of delta-atracotoxin-Hv1 and delta-atracotoxin-Ar1 completely inhibited the binding of the scorpion alpha-toxin AaH II to rat brain synaptosomes as well as the binding of LqhalphaIT, a scorpion alpha-toxin highly active on insects, to cockroach neuronal membranes. Moreover, delta-atracotoxin-Hv1 cooperatively enhanced batrachotoxin binding to rat brain synaptosomes in an analogous fashion to scorpion alpha-toxins. Thus the delta-atracotoxins represent a new class of toxins which bind to both mammalian and insect sodium channels at sites similar to, or partially overlapping with, the receptor binding sites of scorpion alpha-toxins.
Amino Acid Sequence↗
delta-Atracotoxins from australian funnel-web spiders compete with scorpion alpha-toxin binding but differentially modulate alkaloid toxin activation of voltage-gated sodium channels.
delta-Atracotoxins from the venom of Australian funnel-web spiders are a unique group of peptide toxins that slow sodium current inactivation in a manner similar to scorpion alpha-toxins. To analyze their interaction with known sodium channel neurotoxin receptor sites, we studied their effect on [3H]batrachotoxin and 125I-Lqh II (where Lqh is alpha-toxin II from the venom of the scorpion Leiurus quinquestriatus hebraeus) binding and on alkaloid toxin-stimulated 22Na+ uptake in rat brain synaptosomes. delta-Atracotoxins significantly increased [3H]batrachotoxin binding yet decreased maximal batrachotoxin-activated 22Na+ uptake by 70-80%, the latter in marked contrast to the effect of scorpion alpha-toxins. Unlike the inhibition of batrachotoxin-activated 22Na+ uptake, delta-atracotoxins increased veratridine-stimulated 22Na+ uptake by converting veratridine from a partial to a full agonist, analogous to scorpion alpha-toxins. Hence, delta-atracotoxins are able to differentiate between the open state of the sodium channel stabilized by batrachotoxin and veratridine and suggest a distinct sub-conductance state stabilized by delta-atracotoxins. Despite these actions, low concentrations of delta-atracotoxins completely inhibited the binding of the scorpion alpha-toxin, 125I-Lqh II, indicating that they bind to similar, or partially overlapping, receptor sites. The apparent uncoupling between the increase in binding but inhibition of the effect of batrachotoxin induced by delta-atracotoxins suggests that the binding and action of certain alkaloid toxins may represent at least two distinguishable steps. These results further contribute to the understanding of the complex dynamic interactions between neurotoxin receptor site areas related to sodium channel gating.
Animals↗