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Biomedical subjects

A Simons

Publications and source records attributed to A Simons.

At least 19 recordsLinked to original sources

Is objective cure of mild undifferentiated incontinence more readily achieved than that of moderate incontinence? Costs and 2-year outcome.

Because the prognostic value of 1-h pad testing has received scant attention, we tested the hypothesis that mild incontinence of any etiology is more readily cured than moderate incontinence. A consecutive series of 150 patients with mild (2-9.9 g) to moderate (10-49.9 g) incontinence (as judged by weight gain on 1-h pad testing) [1] attending a urogynecology unit were recruited, of whom 145 completed all baseline objective measures: 110 completed 12 weeks of conservative therapy, with follow-up data at 2 years available for 51 subjects. At 12 weeks 81% of 'mild' patients became 'dry' on the 1-h pad test versus 36.8% in the moderate group (chi2<0.0001). Interestingly the post-treatment changes seen in all other outcomes demonstrated equally positive responses for the mild and moderate groups. At 2-year follow-up 29/71 (40.8%) of patients with mild incontinence and 22/74 (29.7%) of patients with moderate incontinence were satisfied and had no requirement for further therapy, the remainder having sought other treatments (chi2=1.963 P=0.161). Of the responders, (11/29) (37.9%) of mildly incontinent patients and (8/22 (36.4%)) of moderately affected subjects remained continent (on 20-point incontinence score < or =2 m, chi2=0.013, P=0.9087). Improvements in quality of life persisted to an equal degree in both groups.

Aged↗

Randomised controlled trial of nurse continence advisor therapy compared with standard urogynaecology regimen for conservative incontinence treatment: efficacy, costs and two year follow up.

OBJECTIVE: To compare the efficacy and labour costs of nurse continence advisors and urogynaecologists in conservative management of urinary incontinence. DESIGN: Single centre randomised controlled trial of patients with mild or moderate leakage. SETTING: Tertiary urogynaecology unit. SAMPLE: One hundred and forty-five consecutive patients with stress and/or urge incontinence. METHODS: Standardised conservative therapy regimens, provided by nurse continence advisors and urogynaecologists. MAIN OUTCOME MEASURE: One-hour pad test, frequency volume charts, a 20-point incontinence score and two quality of life tests, staff treatment times and costs. RESULTS: Of 110 women who completed 12-week treatments, 64% of the women in the nurse continence advisor group (n = 58) and 52% of women treated by urogynaecologists (n = 52) were asymptomatic (dry pad test; OR 1.63, 95% CI 0.71-3.75). There was no significant difference between clinician groups for change in pad test result (P = 0.71), voids/day (0.43), incontinence score (P = 0.57) or quality of life scores (urogenital distress inventory, P = 0.27; Incontinence Impact Questionnaire, P = 0.41). Despite the expected longer consultation times for the advisor group (median 160 min, interquartile range [IQR] 130-210) versus the urogynaecologist group (median 90 min, IQR 60-120), the per capita labour cost for advisor treatment (median AU$59.20, IQR 48.10-77.70) was lower than for treatment given by urogynaecologists (median cost AU$ 189.70, IQR 120.60-250.70, Mann-Whitney U test, P < 0.0001). At 2.5 years, 23/58 patients (40%) treated by advisor and 27/52 patients (52%) treated by urogynaecologist group, who had been cured and discharged, were available for contact. Of these, 29% of women in the nurse continence advisor group and 41% of those treated by urogynaecologists remained continent (on 20-point score). Quality of life improvement persisted equally in both groups. These data should be interpreted cautiously due to a 24% dropout rate. CONCLUSIONS: The reduction in urine leakage and improvement in quality of life observed in patients treated by nurse continence advisors and urogynaecologists were similar at 12 weeks and 2 years, but lower costs arose from treatment provided by nurse advisors. We suggest that conservative treatment by the nurse continence advisor could be used more widely in mild to moderate incontinence.

Aged↗

Safety and efficacy of repeat transradial access for cardiac catheterization procedures.

To determine the safety and efficacy of repeat transradial cardiac catheterization, 1,362 consecutive transradial procedures were examined. Repeat transradial procedures were identified (group I, n = 73) and compared with index procedures (group II, n = 1,289). Baseline patient characteristics, procedure success rates (100% vs. 97.9%; P = NS), complication rates (0% vs. 0.08%; P = NS), and procedure times (23.9 +/- 27.3 min vs. 18.2 +/- 14.7 min; P = NS) were similar between groups. This study suggests that repeat transradial catheterization procedures can be performed safely and successfully in appropriately selected patients.

Aged↗

Thought Field Therapy clinical applications: utilization in an HMO in behavioral medicine and behavioral health services.

Thought Field Therapy (TFT) is a self-administered treatment developed by psychologist Roger Callahan. TFT uses energy meridian treatment points and bilateral optical-cortical stimulation while focusing on the targeted symptoms or problem being addressed. The clinical applications of TFT summarized included anxiety, adjustment disorder with anxiety and depression, anxiety due to medical condition, anger, acute stress, bereavement, chronic pain, cravings, depression, fatigue, nausea, neurodermatitis, obsessive traits, panic disorder without agoraphobia, parent-child stress, phobia, posttraumatic stress disorder, relationship stress, trichotillomania, tremor, and work stress. This uncontrolled study reports on changes in self-reported Subjective Units of Distress (SUD; Wolpe, 1969) in 1,594 applications of TFT, treating 714 patients. Paired t-tests of pre- and posttreatment SUD were statistically significant in 31 categories reviewed. These within-session decreases of SUD are preliminary data that call for controlled studies to examine validity, reliability, and maintenance of effects over time. Illustrative case and heart rate variability data are presented.

Adult↗

Recurrent miscarriage and variant alleles of mannose binding lectin, tumour necrosis factor and lymphotoxin alpha genes.

Variant alleles of the mannose binding lectin (MBL) gene are associated with increased susceptibility to infection and polymorphisms of tumour necrosis factor and lymphotoxin alpha genes (TNF, LTA) are associated with increased severity of infection. Studies have associated recurrent miscarriage with low serum mannose binding lectin concentrations and premature membrane rupture and preterm delivery with elevated maternal and fetal levels of TNF and the TNF (- 308) polymorphism. In this study the frequencies of variant MBL, TNF and LTA alleles in 76 Caucasian couples with idiopathic recurrent miscarriage were compared with those in 69 Caucasian control couples with no history of miscarriage and at least one previous live birth. A new assay based on hybridization to immobilized sequence-specific oligonucleotides (SSO) was used to rapidly detect nine MBL, two TNF and two LTA sequence variants. The assay genotyped all the structural and promoter MBL variants known to influence serum MBL concentrations. This assay was more reliable than restriction digestion or nested allele-specific PCR for the structural variants at codon 54 or 52, respectively. Reliability for codon 57 alleles was not assessed because of the low frequency in this population. The MBL haplotype frequencies in antenatal controls were similar to those reported in other control populations. The frequencies of structural variant MBL genes and of low, medium and high MBL level haplotypes were similar in the recurrent miscarriage and control couples. The TNF and LTA haplotype frequencies were similar in the recurrent miscarriage and control couples. In this carefully defined population no association has been found between recurrent miscarriage and variant alleles of the MBL, TNF or LTA genes.

Abortion, Habitual↗

Establishment of a chemical synthetic lethality screen in cultured human cells.

The synthetic lethality screen is a powerful genetic method for unraveling functional interactions between proteins in yeast. Here we demonstrate the feasibility of a chemical synthetic lethality screen in cultured human cells, based in part on the concept of the yeast method. The technology employs both an immortalized human cell line, deficient in a gene of interest, which is complemented by an episomal survival plasmid expressing the gene of interest, and the use of a novel double-label fluorescence system. Selective pressure imposed by any one of several synthetic lethal metabolic inhibitors prevented the spontaneous loss of the episomal survival plasmid. Retention or loss over time of this plasmid could be sensitively detected in a blind test, while cells were grown in microtiter plates. Application of this method should thus permit high throughput screening of drugs, which are synthetically lethal with any mutant human gene of interest, whose normal counterpart can be expressed. This usage is particularly attractive for the search of drugs, which kill malignant cells in a gene-specific manner, based on their predetermined cellular genotype. Moreover, by replacing the chemicals used in this example with a library of either DNA oligonucleotides or expressible dominant negative genetic elements, one should be able to identify synthetic lethal human genes.

Cell Line, Transformed↗

Adjunctive therapies in the cath lab. Use of combination glycoprotein IIb/IIIa inhibitor and direct thrombin inhibitor drugs to support percutaneous coronary stent placement in a patient with renal insufficiency and heparin-induced thrombocytopenia.

An 81-year-old woman with a history of prior coronary artery bypass surgery, heparin-induced thrombocytopenia with "white clot" syndrome, and renal insufficiency presented with unstable angina. She was referred for cardiac catheterization. Complex percutaneous revascularization of the native circumflex coronary artery was performed using stents. A combination of tirofiban and lepirudin was used with dosing adjusted for renal insufficiency. The hospital course was uncomplicated and the patient was discharged on the fourth hospital day. This is only the second report of the combination use of direct thrombin inhibitor and glycoprotein IIb/IIIa receptor inhibitor.

Aged↗

Frequent loss of 9p21 (p16(INK4A)) and other genomic imbalances in human malignant fibrous histiocytoma.

To search for new recurrent genetic aberrations in malignant fibrous histiocytoma (MFH), a combination of conventional cytogenetic, comparative genomic hybridization (CGH), and Southern blot analyses was applied to a series of 34 tumors. Cytogenetic analysis revealed the presence of multiple structural and numerical aberrations, including marker chromosomes, telomeric associations, double minutes, and ring chromosomes. The most frequent genomic imbalances in this series of neoplasms as detected by CGH were gains of 1q21-q22 (69%), 17q23-qter (41%), and 20q (66%), and losses of 9p21-pter (55%), 10q (48%), 11q23-qter (55%), and 13q10-q31 (55%). Southern blot analyses with p16(INK4A) (CDKN2A; 9p21) and RB1 (13q14) probes provided clear indications for frequent deletions of these tumor suppressor genes, and as such, substantiated the CGH results. Additionally, examination of the TP53 and MDM2 genes showed frequent loss and amplification, respectively. These data indicate that genes involved in the RB1- and TP53-associated cell cycle regulatory pathways may play prominent roles in the development of human MFH.

Blotting, Southern↗

Transradial cardiac catheterization in elderly patients.

The safety and efficacy of transradial cardiac catheterization in elderly patients is unknown. This study examines procedure success rates for transradial catheterization in appropriately selected patients < 70 (n = 195) and >/= 70 (n = 83) years old. Elderly patients were less likely to be selected for the transradial approach (46% vs. 61%; P = 0.05). Although patients >/= 70 years old were more often female (39.7% vs. 24.1%; P = 0.008) and had a smaller body surface area (1.89 +/- 0.18 vs. 2.01 +/- 0.24 m2; P = 0. 001), procedure success rates did not differ (95.1% vs. 94.8%; P = NS). Procedure-related variables including procedure time (15.4 +/- 12.6 vs. 16.1 +/- 11.6 min; P = NS), amount of radiographic contrast (90.1 +/- 31.9 vs. 86.4 +/- 29.8 cc; P = NS), and number of catheters used (1.5 +/- 0.9 vs. 1.5 +/- 0.7; P = NS) were similar between groups. We conclude that transradial catheterization can be safely and effectively performed in selected elderly patients. Cathet. Cardiovasc. Intervent. 51:287-290, 2000.

Adult↗

Attitudes to vaginal/urethral touching and device placement in women with urinary incontinence.

Because of recent development of a number of intravaginal and urethral occlusive devices for the treatment of urinary incontinence, we aimed to develop a linear analog scale that measured women's attitudes to becoming familiar with their genital anatomy and to placing devices into or upon the vagina or urethral orifices. We also investigated whether such attitudes were affected by previous tampon or diaphragm use, or were age dependent. After pilot studies, a 10-item questionnaire was given to 104 consecutive incontinent women, only 30% of whom were quite comfortable about the concept of touching their genitalia: this attitude was age dependent. Only 21% were quite willing to insert a continence device into their vagina: this attitude varied weakly with age but was significantly affected by previous tampon or diaphragm usage. Only 15% felt very comfortable about placing a continence device on to their urethra, but the likelihood of a positive response to this concept was not at all affected by age and was only slightly more common in previous tampon users. Thus older women are less likely to understand the anatomy of their genitalia or to be comfortable about the idea of exploring it, but age is no barrier to willingness to employ urethral or vaginal continence devices per se. We suggest that such a linear analog questionnaire may help gynecologists determine which patients might respond well to the use of vaginal or urethral continence devices.

Adult↗

The relative incidence of detrusor instability and bacterial cystitis detected on the urodynamic-test day.

OBJECTIVE: To determine whether patients with detrusor instability (DI) were more likely to have bacterial cystitis or significant bacteriuria on the urodynamic-test day than were women with a stable bladder. PATIENTS AND METHODS: A catheter specimen of urine was cultured (overnight in air) from 862 consecutive women at the time of urodynamic testing. The upper urinary tract was imaged, with cystoscopy when indicated, to exclude upper tract lesions or malignancy. The percentage of patients with pure idiopathic DI and those with mixed DI/genuine stress incontinence (GSI), in whom the urine culture was positive, was compared with the percentage who had a stable bladder (pure GSI or urodynamically normal) and a positive urine culture, both for the entire dataset and for women aged > or <65 years. Data were also analysed to detect the converse relationship; in those women found to have bacterial cystitis, the relative risk of being found urodynamically unstable or stable was determined. RESULTS: The likelihood of bacterial cystitis occurring in patients with idiopathic DI (5.6%) was significantly greater than that in patients with GSI (1.1%; P = 0.009, Fisher's exact test). The proportion of patients with DI and significant bacteriuria (15. 4%) was significantly greater than that in patients with GSI (7.9%; P = 0.02). In patients with combined pure and mixed DI, bacterial cystitis was significantly more likely to occur (6.3%) than in GSI (P < 0.001), but bacteriuria was no more likely (12.5%, P = 0.09). Conversely, of those women found to have bacterial cystitis, the relative risk of having an unstable bladder was increased (+1.56), but for those with bacteriuria the relative risk of detrusor instability was not increased. CONCLUSION: There was a significant association between idiopathic DI and bacterial cystitis, and we suggest that in some women with an unstable bladder, urinary infection may enhance detrusor contractility. Nevertheless, large-scale studies are needed of the temporal relationship between the onset of bacterial cystitis and the onset of DI.

Adult↗

Isolation and characterization of glioblastoma-associated homozygously deleted DNA fragments from chromosomal region 9p21 suggests involvement of multiple tumour suppressor genes.

Representational difference analysis (RDA) of a human glioblastoma xenograft resulted in the isolation of five tumour-associated homozygously deleted DNA fragments, all originating from chromosome 9, region p21. Subsequent analysis of a series of ten glioblastomas using the newly isolated RDA fragments in conjunction with a series of known 9p21 DNA markers revealed homozygous deletions in nine of the ten (90 per cent) tumours. These deletions encompass the p15/p16 complex and two additional putative tumour suppressor loci. The RDA fragments correspond to the latter two loci. Taken together, these results suggest the involvement of multiple tumour suppressor genes from the 9p21 region in glioblastoma tumourigenesis. The novel RDA fragments will be instrumental in the isolation of the relevant genes.

Animals↗

Transradial cardiac catheterization in patients with prior brachial artery cutdown.

The safety and efficacy of transradial cardiac catheterization in patients with prior ipsilateral brachial cutdown is not known. Using standard techniques we performed transradial catheterization in 278 consecutive patients, of which 63 had prior brachial cutdown. All patients had a strongly palpable radial pulse and a negative Allen's test. Although patients with prior cutdown were older and had a higher incidence of hypertension and prior coronary artery bypass surgery, there was no significant difference in success rates for transradial catheterization (93.6% vs. 95.3%; P = NS). There were no periprocedural complications. Brachial artery occlusion was responsible for only two unsuccessful catheterization attempts. We conclude that, with careful preprocedural screening, ipsilateral transradial cardiac catheterization can be successfully performed in a majority of patients with prior brachial cutdown.

Brachial Artery↗

Ring chromosomes in a malignant mesenchymoma.

We report, for the first time, the cytogenetic and molecular genetic constitution of a human mesenchymoma. As in several other soft tissue sarcomas, supernumerary ring and rod-shaped marker chromosomes were observed next to an otherwise normal diploid karyotype. Comparative genomic in situ hybridization and whole chromosome painting experiments revealed that chromosome 1q21-q25 and 12q14-q15 sequences were amplified, and that these sequences resided on the supernumerary marker chromosomes. We assume that, in this malignant mesenchymoma, the observed chromosomal anomalies may be associated with its well differentiated liposarcomatous component.

Buttocks↗

Efficacy and user acceptability of the urethral occlusive device in women with urinary incontinence.

PURPOSE: We determine the efficacy and user acceptability of the urethral occlusive device (FemAssist) for incontinence for 1 month and identify factors that may predict successful use of the device. MATERIALS AND METHODS: Baseline and posttreatment outcome measures included a 1-hour pad test, frequency volume chart (leakage, voiding and number of pads per 24 hour), visual analog scale for incontinence impact and quality of life (Urogenital Distress Inventory). The last 36 consecutive women also completed a linear analog scale about attitudes toward touching the genitalia. RESULTS: The device was offered to 100 consecutive incontinent women of whom 3 did not enroll in the study and 57 (57%) completed the 1-month trial. Age, incontinence type or severity and attitudes about touching the genitalia were not significantly different between dropouts and participants. Only 13% of recruits were disinclined to place the device on the urethra. Significant reduction of incontinence was observed for all outcome measures with the device in situ. Pad testing revealed that 47% of the patients became continent and 33% had more than 50% benefit, while 9% had worse leakage. Those with severe baseline leakage were equally likely to respond as those with mild or moderate pad test loss. Women with stress, urge or mixed incontinence appeared to respond equally well. CONCLUSIONS: The urethral occlusive device provides a further nonsurgical treatment option which is useful for a range of incontinence types.

Aged↗

A novel chromosomal region of allelic loss, 4q32-q34, in human osteosarcomas revealed by representational difference analysis.

Representational difference analysis (RDA) of a human osteosarcoma xenograft resulted in the isolation of four tumor-associated homozygously deleted DNA fragments, all originating from chromosome 4, region q32-q34. Southern blot analysis using the RDA fragments and interphase FISH analysis using PACs corresponding to these RDA fragments revealed allelic loss of the 4q32-q34 region in 17 of 27 (63%) osteosarcomas tested. These results suggest the involvement of tumor suppressor gene(s) within this chromosomal region in osteosarcoma development. The RDA fragments and corresponding PAC clones will be instrumental in the isolation of such gene(s). Genes Chromosomes Cancer 26:115-124, 1999.

Animals↗

PACT: cloning and characterization of a cellular p53 binding protein that interacts with Rb.

Cellular functions of tumor suppressor proteins can be mediated by protein-protein interactions. Using p53 as a probe to screen an expression library, a cDNA encoding a 250 kDa protein was isolated. Recombinant forms of this protein, designated PACT, bind to wild type p53 while two different mutations abolish this interaction. PACT protein can also interfere with p53 specific DNA binding. PACT contains a serine/arginine (SR) rich region and a C' terminal lysine rich domain. The 250 kDa PACT protein can be precipitated from cell lysates by a method specific for SR proteins. snRNPs can be co-immunoprecipitated from cells with anti-PACT antibodies. These antibodies stain cell nuclei in a speckled pattern reminiscent of the distribution of known splicing factors. Recently, RBQ1, a truncated human homologue of PACT was identified by virtue of Rb binding. We show that RBQ1 is truncated as a result of a possible mutational event. PACT can interact with both cellular Rb and p53.

Alternative Splicing↗