Search PubMed⌕ Search

Biomedical subjects

T J Clark

Publications and source records attributed to T J Clark.

At least 19 recordsLinked to original sources

Characterizing the normal heart using quantitative three-dimensional echocardiography.

We present normative data on cardiac volume, geometry and shape derived using three-dimensional echocardiography (3-DE). Three-dimensional reconstructions were created using the piecewise smooth surface subdivision (PSSS) reconstruction technique of the left and right ventricular (LV and RV) endocardium and the mitral and tricuspid annuli (MA and TA) of 67 normal subjects. We derived LV end-diastolic (ED) and end-systolic (ES) volume indices (VI) of 76.5 +/- 16.8 ml m(-2) and 35.3 +/- 14.1 ml m(-2), LV ejection fraction (EF) of 56.1 +/- 9.93%, RV EDVI and ESVI of 93.2 +/- 20.0 ml m(-2) and 49.9 +/- 13.5 ml m(-2) and RVEF of 47.3 +/- 7.69%, along with data on the geometry and shape of the MA, TA, LV and RV. There was no pattern of consistent understatement or overstatement of volumes or dimensions compared with other imaging modalities, and observed variance in data can largely be accounted for through examination of the physics or protocol of each modality.

Adult↗

Investigating postmenopausal bleeding for endometrial cancer: cost-effectiveness of initial diagnostic strategies.

OBJECTIVE: To determine the most cost-effective outpatient testing strategy for diagnosing endometrial cancer in women with postmenopausal bleeding (PMB). DESIGN: Decision analysis modelling. POPULATION: Women with postmenopausal bleeding. METHODS: A decision analytic model was constructed to reflect current service provision, which evaluated 12 diagnostic strategies using endometrial biopsy (EB), ultrasonography (USS) (4- and 5-mm endometrial thickness cutoff) and hysteroscopy. Diagnostic probability estimates were derived from systematic quantitative reviews, clinical outcomes from published literature and cost estimates from local and NHS sources. MAIN OUTCOME MEASURES: The cost per additional life year gained (pound/LYG) was determined and compared for each diagnostic strategy, and sensitivity analyses were performed. RESULTS: Compared with carrying out no initial investigation, a strategy based on initial diagnosis with USS using a 5-mm cutoff was the least expensive (11,470 pound/LYG). Initial investigation with EB or USS using a 4-mm cutoff was comparably cost-effective (less than 30,000 pound/LYG versus USS with a 5-mm cutoff) at their most favourable diagnostic performance and at disease prevalence of 10% or more. The strategies involving initial evaluation with test combinations or hysteroscopy alone were not cost-effective. CONCLUSIONS: Women presenting for the first time with PMB should undergo initial evaluation with USS or EB.

Aged↗

Accuracy of transvaginal ultrasound in diagnosing endometrial pathology in women with post-menopausal bleeding on tamoxifen.

The incidence of endometrial pathology is increased in women with tamoxifen-induced post-menopausal bleeding (PMB). The aim of this study was to determine the accuracy of transvaginal ultrasound (TVS) in diagnosing endometrial pathology in symptomatic women taking tamoxifen, using endometrial thickness measurements (5 mm and 10 mm cut-offs) and morphological changes within the uterine cavity to define abnormality. The sensitivity of TVS was 97% (95% confidence interval (CI) 83% to 100%) and the specificity 35% (95% CI 17% to 56%) at a 5 mm threshold. The corresponding likelihood ratios for a positive test were 1.47 (95% CI 1.16-2.10) and a negative test were 0.09 (95% CI 0.02-0.53). The use of a higher 10 mm threshold, characterization of endometrial morphology or combining endometrial thickness and morphology did not improve overall accuracy. TVS measurement of endometrial thickness using a 5 mm cut-off is highly accurate in excluding endometrial disease in symptomatic women taking tamoxifen and may negate the need for further diagnostic testing in women unless symptoms recur. A positive TVS result is of little value, so further testing is mandatory in order to detect benign and malignant endometrial disease associated with tamoxifen and PMB.

Breast Neoplasms↗

Patient anxiety and experiences associated with an outpatient "one-stop" "see and treat" hysteroscopy clinic.

BACKGROUND: "One-stop" outpatient hysteroscopy clinics have become well established for the investigation and treatment of women with abnormal uterine bleeding. However, the advantages of these clinics may be offset by patient factors such as anxiety, pain, and dissatisfaction. This study aimed to establish patients' views and experiences of outpatient service delivery in the context of a one-stop diagnostic and therapeutic hysteroscopy clinic, to determine the amount of anxiety experienced by these women and compare this with other settings, and to determine any predictors for patient preferences. METHODS: The 20-item State-Trait Anxiety Inventory was given to 240 women attending a one-stop hysteroscopy clinic: to 73 consecutive women before their appointment in a general gynecology clinic and to 36 consecutive women attending a chronic pelvic pain clinic. The results were compared with published data for the normal female population, for women awaiting major surgery, and for women awaiting a colposcopy clinic appointment. In addition, a questionnaire designed to ascertain patients' views and experiences was used. Logistic regression analysis was used to delineate the predictive values of diagnostic or therapeutic hysteroscopy, and to determine their effect on the preference of patients to have the procedure performed under general anesthesia in the future. RESULTS: Women attending the hysteroscopy clinic in this study reported significantly higher levels of anxiety than those attending the general gynecology clinic (median, 45 vs 39; p = 0.004), but the levels of anxiety were comparable with those of women attending the chronic pelvic pain clinic (median, 45 vs 46; p = 0.8). As compared with the data from the normal female population (mean, 35.7) and those reported for women awaiting major surgery (mean, 41.2), the levels of anxiety experienced before outpatient hysteroscopy clinic treatment were found to be higher (mean, 45.7). Only women awaiting colposcopy (6-item mean score, 51.1 +/- 13.3) experienced significantly higher anxiety scores than the women awaiting outpatient hysteroscopy (6-item mean score, 47.3 +/- 13.9; p = 0.002). Despite their anxiety, most women are satisfied with the outpatient hysteroscopy "see and treat" service. High levels of anxiety, particularly concerning pain but not operative intervention, were significant predictors of patients desiring a future procedure to be performed under general anesthesia. CONCLUSIONS: Outpatient hysteroscopy is associated with significant anxiety, which increases the likelihood of intolerance for the outpatient procedure. However, among those undergoing operative therapeutic procedures, dissatisfaction was not associated with the outpatient setting.

Adult↗

Quality of life instruments in studies of chronic pelvic pain: a systematic review.

The use of quality of life (QoL) instruments in chronic pelvic pain (CPP) will allow a more objective assessment of patient-centred clinical outcomes. However, there is concern that not enough emphasis is placed on clinical face validity (i.e. issues which are of importance to patients and reflect their experiences and concerns). To explore this issue, we performed a systematic review of published research. Relevant papers were identified through electronic scanning of six electronic databases and by manual searching of bibliographies of known primary and review articles. Studies were selected if they assessed women with CPP for life quality, either developing QoL instruments or applying them as an outcome measure. Selected studies were assessed for the quality of their QoL instruments using a 17-item checklist, including 10 items for clinical face validity and seven items for measurement (psychometric) properties. A total of 19 articles were eligible for inclusion in the review. The generic Short Form 36 Health Survey Questionnaire (SF-36) was used most frequently, being employed in 10/19 (53%) of the studies. Three studies developed disease-specific QoL instruments for CPP complying with 59 - 77% of the quality criteria. Overall, quality assessment showed that only 4/18 (22.2%) studies complied with more than half the criteria for face validity, whereas 12/18 (66.6%) studies complied with more than half of the criteria for measurement properties (P = 0.0001). Among existing QoL instruments, compliance with the quality criteria for measurement properties is higher than for clinical face validity. There is a need to develop disease specific QoL instruments for CPP with face validity in addition to sound measurement properties.

Chronic Disease↗

Effect of paper quality on the response rate to a postal survey: a randomised controlled trial. ISRCTN 32032031.

BACKGROUND: Response rates to surveys are declining and this threatens the validity and generalisability of their findings. We wanted to determine whether paper quality influences the response rate to postal surveys METHODS: A postal questionnaire was sent to all members of the British Society of Gynaecological Endoscopy (BSGE). Recipients were randomised to receiving the questionnaire printed on standard quality paper or high quality paper. RESULTS: The response rate for the recipients of high quality paper was 43/195 (22%) and 57/194 (29%) for standard quality paper (relative rate of response 0.75, 95% CI 0.33-1.05, p = 0.1 CONCLUSION: The use of high quality paper did not increase response rates to a questionnaire survey of gynaecologists affiliated to an endoscopic society.

Data Collection↗

Noninvasive techniques to detect fetal anemia due to red blood cell alloimmunization: a systematic review.

OBJECTIVE: To estimate, in maternal red blood cell alloimmunization, the diagnostic value of fetal ultrasonography and Doppler blood flow velocity in the evaluation and prediction of fetal anemia. METHODS: Literature from 1970 to 2000 was identified using general bibliographic databases (MEDLINE and EMBASE), the Cochrane Library and relevant specialist register of the Cochrane Collaboration, and by checking reference lists of known primary and review articles. Studies were selected if the accuracy of the fetal ultrasound parameters or Doppler studies of blood flow in the fetal vessels was estimated compared with a reference standard (fetal hemoglobin). The diagnostic tests evaluated were ultrasound measurement of the fetal spleen perimeter and Doppler studies of blood velocity estimates in the umbilical vein, ductus venosus, middle cerebral artery, thoracic aorta, and umbilical vessel combined with the thoracic aorta. Study selection, quality assessment, and data abstraction were performed independently and in duplicate. Data from the selected studies were abstracted as 2 x 2 tables comparing the diagnostic test result with the reference standard. Diagnostic accuracy was expressed as likelihood ratios. RESULTS: The review included eight primary studies with 362 pregnancies affected by red cell alloimmunization. Prospective patient recruitment and complete population details were reported in half of the selected studies (four of eight). Only one study reported masking the diagnostic test results to clinicians. The diagnostic test performance varied widely according to the type of the test evaluated and the cutoff level used to define fetal anemia, which varied from study to study. The diagnostic test study of highest methodological quality reported a positive likelihood ratio of 8.45 (95% confidence interval 4.69, 15.56) and negative likelihood ratio of 0.02 (95% confidence interval 0.001, 0.25) for maximum middle cerebral artery Doppler velocity. CONCLUSION: The literature reporting noninvasive techniques to predict fetal anemia is methodologically poor and a standard approach to the evaluation of these techniques is lacking. A recommendation for practice cannot be generated without further rigorous research.

Blood Flow Velocity↗

Accuracy of outpatient endometrial biopsy in the diagnosis of endometrial hyperplasia.

BACKGROUND: To determine the accuracy of outpatient endometrial biopsy in diagnosing endometrial hyperplasia in women with abnormal uterine bleeding. DESIGN: Systematic quantitative review of published medical literature. DATA SOURCES: Relevant papers were identified through electronic scanning of MEDLINE (1980-1999) and EMBASE (1980-1999), manual searching of bibliography of known primary and review articles and contact with manufacturers. REVIEW METHODS: Studies were selected if accuracy of outpatient endometrial biopsy, in women with abnormal pre or postmenopausal uterine bleeding, was estimated compared to a reference standard, which was endometrial histology obtained by tissue sampling under anesthesia. Quality assessment and data extraction were performed in duplicate. Diagnostic accuracy was determined by pooled likelihood ratios (LR) for positive and negative test results for endometrial hyperplasia. RESULTS: There were 881 subjects in 8 diagnostic evaluations reported in 6 primary studies. Postmenopausal women represented 25% of the participants studied. There were 43 patients in whom outpatient sampling was inadequate. A positive test result on outpatient biopsy diagnosed endometrial hyperplasia with a pooled LR of 12.0 (95% CI 7.8-18.6) while a negative test result had a pooled LR of 0.2 (95% CI 0.1-0.3). With a positive test result, the posttest probability of endometrial hyperplasia was 57.7% (95% CI 41.1%-72.7%) while it was 2.2% (95% CI 0.9%-4.1%) with a negative test. CONCLUSION: Outpatient endometrial biopsy has modest accuracy in diagnosing endometrial hyperplasia. Therefore, additional endometrial assessment should be undertaken, especially if symptoms persist or intrauterine structural abnormalities are suspected.

Ambulatory Care↗

Hysterectomy with bilateral salpingo-oophorectomy: a survey of gynecological practice.

BACKGROUND: Oophorectomy at the time of hysterectomy can be carried out by open and minimally invasive methods. The objective of this survey was to determine the current operative practice concerning oophorectomy at hysterectomy for benign gynecological disease in the UK, and to establish practitioners' views regarding the desirability of a randomized controlled clinical trial to compare various operative techniques for this procedure. SETTING: Gynecologists associated with the British Society of Gynecological Endoscopy. METHODS: A self-administered structured questionnaire was posted to 323 UK gynecologists to enquire about their surgical practice in performing oophorectomy at hysterectomy and their willingness to participate in a randomized trial. RESULTS: The postal questionnaire was returned by 147 (46% response rate). For performing oophorectomy at hysterectomy, 84 (57%) routinely used laparotomy only. However, 67 (46%) in total were competent in all surgical methods i.e. laparotomy, vaginal and laparoscopical. Of these, 38 (57%) were willing to enter patients into a proposed clinical trial comparing vaginal and laparoscopically assisted oophorectomy at hysterectomy. CONCLUSION: The current surgical approach to performing oophorectomy at hysterectomy varies widely. This suggests that opinion regarding the relative roles of abdominal, vaginal and laparoscopic methods is divided. Hence, a rigorous randomized trial comparing the efficacy and safety of these methods is practicable and urgently needed.

Aged↗

Mutations in catB, the gene encoding muconate cycloisomerase, activate transcription of the distal ben genes and contribute to a complex regulatory circuit in Acinetobacter sp. strain ADP1.

Mutants of the bacterium Acinetobacter sp. strain ADP1 were selected to grow on benzoate without the BenM transcriptional activator. In the wild type, BenM responds to benzoate and cis,cis-muconate to activate expression of the benABCDE operon, which is involved in benzoate catabolism. This operon encodes enzymes that convert benzoate to catechol, a compound subsequently degraded by cat gene-encoded enzymes. In this report, four spontaneous mutants were found to carry catB mutations that enabled BenM-independent growth on benzoate. catB encodes muconate cycloisomerase, an enzyme required for benzoate catabolism. Its substrate, cis,cis-muconate, is enzymatically produced from catechol by the catA-encoded catechol 1,2-dioxygenase. Muconate cycloisomerase was purified to homogeneity from the wild type and the catB mutants. Each purified enzyme was active, although there were differences in the catalytic properties of the wild type and variant muconate cycloisomerases. Strains with a chromosomal benA::lacZ transcriptional fusion were constructed and used to investigate how catB mutations affect growth on benzoate. All of the catB mutations increased cis,cis-muconate-activated ben gene expression in strains lacking BenM. A model is presented in which the catB mutations reduce muconate cycloisomerase activity during growth on benzoate, thereby increasing intracellular cis, cis-muconate concentrations. This, in turn, may allow CatM, an activator similar to BenM in sequence and function, to activate ben gene transcription. CatM normally responds to cis,cis-muconate to activate cat gene expression. Consistent with this model, muconate cylcoisomerase specific activities in cell extracts of benzoate-grown catB mutants were low relative to that of the wild type. Moreover, the catechol 1,2-dioxygenase activities of the mutants were elevated, which may result from CatM responding to the altered intracellular levels of cis,cis-muconate and increasing catA expression. Collectively, these results support the important role of metabolite concentrations in controlling benzoate degradation via a complex transcriptional regulatory circuit.

Acinetobacter↗

Surgical correction of congenital uterine anomalies.

Congenital uterine abnormalities have been associated with poor reproductive outcome. Anatomical corrections utilizing open or endoscopic surgery has been recommended to improve these outcomes. This article assesses the available evidence.

Abortion, Spontaneous↗

Pruritus in pregnancy and obstetric cholestasis.

Pruritus is often considered a common but minor symptom of pregnancy. However, pruritus caused by obstetric cholestasis is increasingly being recognized as a cause of so-called 'unexplained' stillbirths. This article reviews recent literature and outlines possible management strategies with the aim of reducing maternal morbidity and improving perinatal outcome.

Cholagogues and Choleretics↗

Response of vulvar lichen sclerosus and squamous cell hyperplasia to graduated topical steroids.

OBJECTIVE: To determine whether symptomatic remission could be obtained equally effectively in patients with vulvar lichen sclerosus, squamous cell hyperplasia or mixed disease in response to a standardized course of graduated topical steroids. STUDY DESIGN: A retrospective analysis of 137 patients with biopsy-proven lichen sclerosus (84), squamous cell hyperplasia (42) or mixed disease (11) treated between 1990 and 1997 with a standard, three-month regimen of graduated topical steroids was carried out. Presence or absence of symptoms and side effects of treatment were recorded three and six months following induction of the initial graduated topical steroid regimen. RESULTS: On completion of the graduated topical steroid course, 59% of patients were asymptomatic (P = .035), and at six months, 58% were asymptomatic (P = .11). Remission of symptoms was more easily achieved in patients with lichen sclerosus as compared to patients with squamous cell hyperplasia and mixed disease at both three and six months (P = .09 at three and P = .035 at six). Four cases of local reactions to the steroids were recorded, as were two cases of vulvar malignancy. CONCLUSION: Symptomatic remission was significantly easier to achieve in patients with vulvar lichen sclerosus as compared to those with squamous cell hyperplasia following treatment with graduated topical steroids.

Administration, Topical↗

New approaches for the analysis of molecular recognition using the IAsys evanescent wave biosensor.

Trends in the analysis of molecular recognition using the IAsys evanescent wave biosensor are outlined. Diversification of sensor surface chemistry, an open cuvette format and the advent of robotics controlled by intelligent software are widening the range and throughput of applications. Analyses of binding and dissociation are now carried out across a wide spectrum of biomolecules, including protein, nucleic acid, carbohydrate and lipid. Determinations are obtained from a range of experimental formats. These include qualitative 'yes/no' screening assays, through semi quantitative ranking of kinetic association, dissociation and equilibrium constants for a family of binding partners, to deriving constants comparable with those which would be obtained in free solution. A dependence of the initial rate of biomolecular association on concentration allows analyte concentration to be measured--an increasingly common application class. This is often employed in situations where a rapid determination is required The ability to recover bound analyte from the sensor surface in sufficient amounts for subsequent characterization is opening up new routes to the parallel analysis of structure and function.

Animals↗