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D Gordon

Publications and source records attributed to D Gordon.

At least 109 records · Page 6Linked to original sources
PubMed1999

NMR structures and activity of a novel alpha-like toxin from the scorpion Leiurus quinquestriatus hebraeus.

NMR structures of a new toxin from the scorpion Leiurus quinquestriatus hebraeus (Lqh III) have been investigated in conjunction with its pharmacological properties. This toxin is proposed to belong to a new group of scorpion toxins, the alpha-like toxins that target voltage-gated sodium channels with specific properties compared with the classical alpha-scorpion toxins. Electrophysiological analysis showed that Lqh III inhibits a sodium current inactivation in the cockroach axon, but induces in addition a resting depolarization due to a slowly decaying tail current atypical to other alpha-toxin action. Binding studies indicated that radiolabeled Lqh III binds with a high degree of affinity (Ki=2.2 nM) on cockroach sodium channels and that the alpha-toxin from L quinquestriatus hebraeus highly active on insects (LqhalphaIT) and alpha-like toxins compete at low concentration for its receptor binding site, suggesting that the alpha-like toxin receptor site is partially overlapping with the receptor site 3. Conversely, in rat brain, Lqh III competes for binding of the most potent anti-mammal alpha-toxin from Androctonus australis Hector venom (AaH II) only at very high concentration. The NMR structures were used for the scrutiny of the similarities and differences with representative scorpion alpha-toxins targeting the voltage-gated sodium channels of either mammals or insects. Three turn regions involved in the functional binding site of the anti-insect LqhalphaIT toxin reveal significant differences in the Lqh III structure. The electrostatic charge distribution in the Lqh III toxin is also surprisingly different when compared with the anti-mammal alpha-toxin AaH II. Similarities in the electrostatic charge distribution are, however, recognized between alpha-toxins highly active on insects and the alpha-like toxin Lqh III. This affords additional important elements to the definition of the new alpha-like group of scorpion toxins and the mammal versus insect scorpion toxin selectivities.

Amino Acid Sequence↗
PubMed1999

Development of postoperative urinary stress incontinence in clinically continent patients undergoing prophylactic Kelly plication during genitourinary prolapse repair.

The present study was undertaken to evaluate the efficacy of Kelly plication in preventing postoperative urinary stress incontinence in clinically continent patients undergoing surgery for genitourinary prolapse. Thirty clinically continent patients with grade-3 genitourinary prolapse were found to have a positive stress test with repositioning of the prolapse during preoperative urodynamic evaluation. In addition to the genitourinary prolapse repair, these patients underwent a Kelly plication as a preventive measure against possible development of postoperative urinary stress incontinence. Postoperative follow-up included a detailed urogynecologic questionnaire, pelvic examination, urine culture, Q-tip cotton swab test, and a full urodynamic evaluation. The mean duration of follow-up was 25.5 +/- 14.1 months. Fifteen (50%) patients developed subjective and objective postoperative stress incontinence. Eleven (37%) patients developed objective postoperative stress incontinence (proven by urodynamic evaluation) with no subjective complaints of stress incontinence. Prophylactic Kelly plication as performed by the method described does not appear to be effective in preventing postoperative urinary stress incontinence in clinically continent patients who undergo surgery for genitourinary prolapse.

Evaluation Studies as Topic↗
PubMed1999

Anal incontinence: prevalence among female patients attending a urogynecologic clinic.

The present study prospectively surveyed the prevalence of anal incontinence among 283 consecutive female patients attending a urogynecologic outpatient clinic in a maternity hospital. Data concerning bowel habits, laxative use, previous anorectal surgery, and the presence, severity, and frequency of anal incontinence were collected by interviewing the patients. Anal incontinence was reported by 83 women, representing 29% of the study population. Of those reporting anal incontinence, 30% (9% of the study population) were incontinent to solid feces, 22% (6%) to liquid feces, and 48% (14%) to gas. Age distribution demonstrates progressive rise and a high prevalence of anal incontinence in patients older than 60 years. A significant higher rate of vacuum deliveries was found among patients with anal incontinence, compared with continent patients (9.6% vs. 2.5%; P = 0.01). Increased prevalence of anal incontinence was also found among patients with past history of hemorrhoidectomy and those with urodynamic diagnosis of combined genuine stress incontinence and detrusor instability/sensory urgency. In conclusion, in patients attending a urogynecologic clinic, anal incontinence is a frequent, although rarely volunteered, symptom.

Adult↗
PubMed1999

Stress urinary incontinence: prevalence among nulliparous compared with primiparous and grand multiparous premenopausal women.

The study was conducted to assess the prevalence of stress urinary incontinence in premenopausal nulliparae, primiparae, and grand multiparae, and to examine possible obstetric risk factors. Three hundred consecutive nulliparae, primiparae, and grand multiparae, 20 to 43 years of age, were interviewed during the third postpartum day of their consequent delivery about the symptom of stress urinary incontinence. Women were asked whether they had experienced stress urinary incontinence before, during, or after previous pregnancies and how troubled they were by their incontinence. Details of general and gynecologic history, parity, mode of previous deliveries, and birth weights were sought. Main outcome measures included prevalence of pregnancy-related and (persistent) nonpregnancy-related stress urinary incontinence. Prevalence of persistent stress urinary incontinence was significantly higher in grand multiparae compared with nulliparae (21% vs. 5%, respectively; P = 0.0008). Prevalence of persistent stress urinary incontinence among grand multiparae who had been delivered of at least one baby weighing more than 4,000 g was significantly higher than in those who did not (29.4% vs. 16.7%, respectively). The birth weight of the first newborn and operative vaginal delivery were not found to be associated with increased risk of stress urinary incontinence. Grand multiparity was found to be associated with an increased risk of developing persistent stress urinary incontinence during reproductive ages. The delivery of at least one baby weighing more than 4,000 g seems to be a predominant factor. Neurourol. Urodynam. 18:419-425, 1999.

Adult↗
PubMed1999

Comparison of empirical strategies to maximize GENEHUNTER lod scores.

We compare four strategies for finding the settings of genetic parameters that maximize the lod scores reported in GENEHUNTER 1.2. The four strategies are iterated complete factorial designs, iterated orthogonal Latin hypercubes, evolutionary operation, and numerical optimization. The genetic parameters that are set are the phenocopy rate, penetrance, and disease allele frequency; both recessive and dominant models are considered. We selected the optimization of a recessive model on the Collaborative Study on the Genetics of Alcoholism (COGA) data of chromosome 1 for complete analysis. Convergence to a setting producing a local maximum required the evaluation of over 100 settings (for a time budget of 800 minutes on a Pentium II 300 MHz PC). Two notable local maxima were detected, suggesting the need for a more extensive search before claiming that a global maximum had been found. The orthogonal Latin hypercube design was the best strategy for finding areas that produced high lod scores with small numbers of evaluations. Numerical optimization starting from a region producing high lod scores was the strategy that found the highest maximum observed.

Alcoholism↗
PubMed1999

Power loss for multiallelic transmission/disequilibrium test when errors introduced: GAW11 simulated data.

Many researchers are considering the use of transmission/disequilibrium tests (TDT) for trios of genotypes (father, mother, child) as a method for localizing genes associated with complex diseases. We evaluate the effect of random errors (allele changes) in trios on the power to detect linkage. For a marker in the simulated data set, one allele is associated with the fictitious disease in a certain subpopulation. For the data as given (no errors), our power to detect linkage using the multiallelic TDT (TDTmhet) is 68% (critical p-value set at 0.0001). We introduce errors into trios at various rates (1%, 5%, or 10%), remove only trios displaying mendelian inconsistencies, and recalculate power to detect linkage. Our principal finding is that there is power loss to detect linkage with the TDTmhet when errors are introduced. We observe power losses of 8%, 16%, and 48% for error rates of 1%, 5%, and 10%, respectively. To determine the source of the power loss, we perform Monte Carlo simulations. At the 1% and 5% rates, we conclude that power loss is due primarily to loss in sample size. At the 10% rate, we observe substantial power loss due to error introduction in addition to sample size reduction. We also determine, given a particular error rate, the probability that we detect errors if we use only mendelian consistency as a check. We find that the mean detection rates for the data sets with 1%, 5%, or 10% error rates are 58%, 60%, and 62%, respectively. As a result, the apparent error rate appears to be almost half the true error rate. Based on these results, we recommend that researchers maintain error rates below 5% when using the TDTmhet for linkage, use additional methods beyond mendelian consistency checks when searching for errors in their data, and modify sample size calculations when accounting for errors in their genotype data.

Alleles↗
PubMed1999

Isolated splenic metastasis from colorectal carcinoma: report of a case and review of the literature.

In general, surgical resection for metastatic colorectal adenocarcinoma rarely benefits more than a small percentage of patients long term. In the case of isolated splenic metastasis without evidence of other metastatic disease, splenectomy may increase survival times in patients with previously resected colorectal adenocarcinoma. Currently there are only five case reports involving isolated splenic metastases in the English-language literature. This article presents a sixth case and a review of the previous five cases in the literature, with a discussion on the possible diagnostic and therapeutic approaches to these rare but important cases and the apparently significant survival advantage of early diagnosis and treatment.

Adenocarcinoma↗
PubMed1999

Sexual function in women attending a urogynecology clinic.

The study prospectively evaluated the relationship between sexual dysfunction and urodynamic diagnoses in 100 consecutive female patients referred for urogynecologic evaluation. Sexual function was evaluated by a detailed questionnaire that addressed four phases of the sexual cycle: desire, arousal, orgasm and satisfaction. Each phase of the sexual cycle was assessed separately using a score of 1-4. Total sexual function (TSF) score was calculated by combining the scores of the four examined parameters (range 4-16). Analysis revealed statistically significant (P < 0.05) lower TSF scores in patients with detrusor instability (DI) than in those with genuine stress incontinence, sensory urge or mixed urodynamic diagnoses (8.65 +/- 4 versus 12.22 + 3.6, 10.25 +/- 4.1 and 11.47 +/- 4.1, respectively). Three per cent of the elderly women (>60 years) compared to 29% of the younger women (< or = 60 years) reported urinary incontinence during sexual activity. Sexual function should therefore be routinely evaluated in women presenting with urinary symptoms.

Adult↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗