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Biomedical subjects

D Gordon

Publications and source records attributed to D Gordon.

At least 91 records · Page 5Linked to original sources
PubMed1999

Prostate cancer expression profiling by cDNA sequencing analysis.

Prostate cancer is a frequently diagnosed solid tumor that is originated mostly from prostate epithelium. One of the key issues in prostate cancer research is to develop molecular markers that can effectively detect and distinguish the progression and malignancy of prostate tumors. Automated, single-pass cDNA sequencing was utilized to rapidly identify expressed genes in a number of cDNA libraries constructed from various normal and tumor prostatic tissues. These included cell lines as well as short-term epithelial culture. A total of 6604 expressed sequence tags (ESTs) were generated and searched against on-line nucleotide and protein databases. A relational database centric software system was constructed to process, store, and analyze EST data rapidly. cDNA contigs were also obtained by assembly of multiple EST sequences. Protein structural signatures were annotated using motif analysis tools including BLOCKS and an in-house-designed neural network. Cross-library comparisons revealed their unique gene expression profiles. Several differentially expressed cDNA clones were identified, and their expression patterns were confirmed by RNA dot blot and RT-PCR analyses.

Cell Line↗
PubMed1999

[Pelvic floor exercise and biofeedback in women with urinary stress incontinence].

Stress urinary incontinence is a medical and social problem. In the past decade there has been increased awareness of this condition and the number of those affected who seek help is increasing. Treatment is usually surgical-elevation of the bladder neck. Pelvic floor exercise is an accepted conservative treatment modality used for mild to moderate cases who have not yet completed their families. We present our results in 30 women, aged 28-71 years, av. 49% with genuine stress incontinence treated with pelvic floor exercise and biofeedback. 14 patients (46.7%) were completely cured and 15 (50%) were improved. In only 1 was there no improvement. Our results show significant improvement in the duration and intensity of pelvic floor contractions after treatment. Pelvic floor exercise with biofeedback is a very important treatment modality, requiring a highly motivated patient and a physiotherapist specialized in pelvic floor exercise.

Adult↗
PubMed1999

Lifetime prevalence, characteristics, and associated problems of non-consensual sex in men: cross sectional survey.

OBJECTIVE: To identify the lifetime prevalence of non-consensual sexual experiences in men, the relationship between such experiences as a child and as an adult, associated psychological and behavioural problems, and help received. DESIGN: Cross sectional survey. SETTING: England. SUBJECTS: 2474 men (mean age 46 years) attending one of 18 general practices. MAIN OUTCOME MEASURES: Experiences of non-consensual and consensual sex before and after the age of 16 years-that is, as a child and adult respectively-psychological problems experienced for more than 2 weeks at any one time, use of alcohol (CAGE questionnaire), self harm, and help received. RESULTS: 2474 of 3142 men (79%) agreed to participate; 71/2468 (standardised rate 2.89%, 95% confidence interval 2.21% to 3.56%) reported non-consensual sexual experiences as adults, 128/2423 (5.35%, 4.39% to 6.31%) reported non-consensual sexual experiences as children, and 185/2406 (7.66%, 6.54% to 8.77%) reported consensual sexual experiences as children that are illegal under English law. Independent predictors of non-consensual sex as adults were reporting male sexual partners (odds ratio 6.0, 2.6 to 13.5), non-consensual sex in childhood (4.2, 2.1 to 8.6), age (0.98, 0.96 to 0.99), and sex of interviewer (2.0, 1.2 to 3.5). Non-consensual sexual experiences were associated with a greater prevalence of psychological problems, alcohol misuse, and self harm. These sexual experiences were also significant predictors of help received from mental health professionals. CONCLUSION: Almost 3% of men in England report non-consensual sexual experiences as adults. Medical professionals need to be aware of the range of psychological difficulties in men who have had such experiences. They also need to be aware of the relationship between sexual experiences in childhood and adulthood in men.

Adolescent↗
PubMed1999

The putative bioactive surface of insect-selective scorpion excitatory neurotoxins.

Scorpion neurotoxins of the excitatory group show total specificity for insects and serve as invaluable probes for insect sodium channels. However, despite their significance and potential for application in insect-pest control, the structural basis for their bioactivity is still unknown. We isolated, characterized, and expressed an atypically long excitatory toxin, Bj-xtrIT, whose bioactive features resembled those of classical excitatory toxins, despite only 49% sequence identity. With the objective of clarifying the toxic site of this unique pharmacological group, Bj-xtrIT was employed in a genetic approach using point mutagenesis and biological and structural assays of the mutant products. A primary target for modification was the structurally unique C-terminal region. Sequential deletions of C-terminal residues suggested an inevitable significance of Ile73 and Ile74 for toxicity. Based on the bioactive role of the C-terminal region and a comparison of Bj-xtrIT with a Bj-xtrIT-based model of a classical excitatory toxin, AaHIT, a conserved surface comprising the C terminus is suggested to form the site of recognition with the sodium channel receptor.

Amino Acid Sequence↗
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↗