Biomedical subjects
Publications and source records attributed to M Fordham.
A series of simple tests have been used to measure the performance of flat-bed film scanners suitable for digitisation of electron micrographs. Two of the film scanners evaluated are commercially available and one has been constructed in the laboratory paying special attention to the needs of the electron microscopist. The tests may be useful for others.
Heat shock proteins (hsps) occupy a central role in the regulation of intracellular homeostasis, and differential expression of individual hsps occurs in a broad range of neoplastic processes. This study was performed to test the hypothesis that the particular patterns by which individual hsps become specifically modulated in human prostate cancers are correlated with behavioral phenotype and hence may be of value in determining the most appropriate clinical management of individual patients. Monoclonal antibodies specific for each hsp protein were used to assess expression of hsp27, hsp60, and hsp70 in formalin-fixed, paraffin wax-embedded, archival tissue specimens of early prostatic adenocarcinomas (pT1-2N0M0) removed at radical prostatectomy (n = 25) and in advanced cancers (n = 95) identified at transurethral resection of prostate (TURP). These findings were compared with similar data from control prostates (n = 10) removed at primary cystectomy for urinary bladder neoplasia not involving the prostate and also at TURP for benign prostatic hyperplasia (n = 50). Western blotting of whole cell lysates derived from established human prostatic epithelial cell lines PNT2, LNCaP, DU145, and PC3 was compared with expression of hsps by the primary human tissues. This study found that early in situ neoplastic transformation of normal prostatic epithelium was consistently associated with loss of hsp27 expression and that the level of hsp27 expression by individual prostate cancers was correlated with their Gleason grade. In advanced cancers, hsp27 expression was invariably associated with poor clinical outcome (P = 0.0001). Data from cell lines supported the primary tissue findings, with elevated hsp27 expression only in aggressive malignant cell lines and androgen-insensitive cell lines. Expression of hsp60 was significantly increased in both early and advanced prostate cancer when compared with nonneoplastic prostatic epithelium (P < 0.0001), as well as in malignant prostate cancer cell lines. Expression of hsp70 was unaltered in early prostate cancers when compared with nonneoplastic prostatic epithelium but showed a diminished expression in morphologically advanced cancers (P = 0.0029). No consistent correlation was found between levels of hsp60 or hsp70 expression and phenotypic behavior of individual primary prostatic cancers. Thus, patterns of hsp expression have been confirmed to be specifically and consistently modulated in both early and advanced human prostate cancers. Whereas absence of hsp27 is a reliable objective marker of early prostatic neoplasia, reexpression of this protein by an individual invasive prostatic carcinoma invariably heralds poor clinical prognosis. Because this protein has been shown to alter the balance between proliferation and apoptosis, understanding the mechanism(s) by which individual hsps regulate intracellular homeostasis may assist in explaining some key processes that occur during evolution of human prostate cancers. We suggest that hsp27 expression provides novel diagnostic and prognostic information on individual patient survival which, if obtained at the time of primary diagnosis, would assist in determining tumor-specific management strategies. Development of techniques to therapeutically modulate hsp27 expression raises the possibility of novel targeted approaches to regulate this homeostatic mechanism, thus allowing better control over tumor cell proliferation and hence patient survival.
The author discussed various advanced roles for the perioperative RN; commitment and passion for the OR professional; the need for education, education, education; and how to plan your career.
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OBJECTIVE: To determine the effectiveness of prostatectomy in reducing symptom severity and bother and in improving disease-specific and general quality of life. PATIENTS AND METHODS: A prospective, cohort study was performed in National Health Service and private hospitals in the Northern, Wessex, Mersey, and South-West Thames Health Regions which comprised 5276 men undergoing prostatectomy recruited by 101 of the 106 (96%) surgeons (specialist and non-specialist) performing prostatectomy during a 6-month period. Patients were assessed using the American Urological Association (AUA) Symptom Index Score, the AUA symptom bother score, disease-specific and generic quality-of-life scores, the occurrence of adverse events (urinary incontinence, erectile impotence and retrograde ejaculation) and three global (general) questions on the results of their treatment. The outcome was assessed 3 months after surgery. RESULTS: Prostatectomy was effective in reducing both symptoms (initial mean score 20.1 reduced to 7.4, P < 0.001) and symptom bother (initial mean score 14.4 reduced to 4.3, P < 0.001). Not all men experienced a good reduction in symptoms; 121 (3.9%) were worse, 301 (9.6%) were the same, and 721 (23%) experienced only slight improvement. The type of operation, grade of principal operator and use of pre-operative investigations were not associated with the extent of symptomatic improvement. Changes in symptom severity were highly correlated with changes in bothersomeness++ and disease-specific quality of life but not with generic quality of life. A third of men who were continent before surgery reported some incontinence 3 months later, although only 6% found it a problem. Two-thirds of men experienced retrograde ejaculation and 31% experienced some erectile impotence following surgery. CONCLUSIONS: Prostatectomy is effective in reducing symptoms in most men. Men who experience a substantial reduction in symptoms were more likely to report a favourable outcome. The study confirmed that approximately one-third of men reported an unfavourable result 3 months after their operation.
OBJECTIVE: To determine everyday practice in the hospital management of men undergoing prostatectomy and the extent of its variation. PATIENTS AND METHODS: A total of 5361 patients, who represented 89% of all those undergoing prostatic procedures in four health regions (Mersey, Wessex, Northern and South West Thames) and one test site (within Trent) were recruited by 103 (97%) surgeons. Clinical information was collected on a pre-coded data collection form which was completed during the hospital stay by the principal operator. Patient identification occurred at the time of surgery. RESULTS: Important findings included: (i) both older men and those of higher social class were more likely to undergo prostatectomy with fewer symptoms; (ii) men who waited longer for surgery had worse symptoms by the time of their operation; (iii) there were unexplained differences in routine pre- and post-operative investigation and treatment. Half the men had their flow rate or residual urine measured as part of their pre-operative assessment. About half the men received prophylactic antibiotics; (iv) when large groups were analysed, a consistent proportion of men throughout the study (12%) were undergoing the operation for a second time. The clinical course of men having a repeat operation differed in many ways from those having a first time procedure; (v) the larger proportion of men (62%) had surgery for strong indications as opposed to symptoms alone; (vi) although most operations were performed by consultants, emergency admissions, though symptomatically more severe and sicker, were more likely to be operated on by trainee surgeons; (vii) significant variation in mean pre-operative symptom severity and bother scores were seen between surgeons. CONCLUSION: The clinical management of prostatectomy has been defined in a large and representative UK sample. In some circumstances consistent variations have been identified. It is not yet clear whether these variations influence outcome. These data can be used by surgeons wishing to compare their own patient management with that described here.
Objective--To determine the feasibility of performing multicentre process and outcome audits of common interventions taking prostatic procedures as an example. Design--Prospective, cohort study. Setting--All National Health Service and independent hospitals in Northern, Wessex, Mersey, and South West Thames health regions. Patients--5361 men undergoing prostatectomy identified by 103 of the 107 urologists and general surgeons performing prostatectomy in the study regions. Main measures-- Rates of participation by surgeons and patients; completeness of clinical data provided by surgeons; patient response rate and completeness of patient derived data; and cost. Results--Most surgeons (103,96%) agreed to participate. Overall, the proportion of eligible patients invited to take part was high (89%), although this was only measured in South West Thames, where dedicated data collectors were employed. Few men (80, 1.5%) declined to participate. Of those surviving for three months after surgery, 82.4% (4226) completed and returned the postal questionnaire. The response rate was higher in South West Thames (86.7%) than in the other regions (80.6%-80.8%). The audit was well received: 91% of patients found the questionnaire easy to complete and only 2.3% of them disapproved. Completeness of data was high with both the hospital and patient questionnaires. Missing data occurred in less than 5% of responses to most questions. The attributable cost was 34.50 pounds per patient identified or 44 pounds for patients in whom either the treatment outcome or vital status was known three months after their prostatectomy. Conclusions--This multicentre audit of process and outcome of prostatectomy proved feasible in terms of surgeon participation, patient identification, and the quantity and quality of data collection. Whether the cost was warranted will depend on how surgeons use the audit data to modify their practice.
There is increasing interest in the acquisition and measurement of physical fitness in general populations (Bassey and Fentem 1981). Measuring fitness can be uncomfortable and exhausting for subjects and expensive and time-consuming for experimenters (Andersen et al. 1971). Various authors have described and/or evaluated methods for the prediction of VO2 max (Astrand and Rhyming 1954, Davies 1968, Fitchett 1985, Harrison et al. 1980, Jette 1979, Jette et al. 1982, Shephard 1975, Shephard et al. 1979). A valid, safe, socially-acceptable alternative for such measurements applicable to a population would be of benefit. Asking subjects how they perceive their own physical fitness might be such an alternative. The validity and reliability of the data contained from such a questionnaire could be tested against conventional measures of physical fitness. A study which incorporated questionnaire surveys as one method of determining physical fitness in a large population was undertaken on Fire Service personnel in England, Scotland, and Wales (Ellam et al. 1985); a subsample of the population were questioned in the same way but in addition their fitness was assessed by physiological measurements. This paper describes the characteristics of the physical fitness of an average fireman as revealed by responses to questionnaires and how firemen felt their fitness was related to their working duties; it further examines these in relation to objective measurements.
This paper starts from recommendations of Freud and Jung on the desirable attitudes of analysts to their patients, and especially open-mindedness which I have named 'not knowing beforehand'. I use the metaphor of a filing cabinet to illustrate how to empty one's mind and, so to speak, lock up one's knowledge, memory, and desires in that filing cabinet. That gives space for the patient to structure his interview. I illustrate how knowing beforehand can disrupt an interview and how 'filing-cabinet material' will get used when tailored to the interview structure. The metaphor is used for the sake of simplicity. It does not include the complexity of the analytical dialectic.
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Scanning confocal microscopes offer improved rejection of out-of-focus noise and greater resolution than conventional imaging. In such a microscope, the imaging and condenser lenses are identical and confocal. These two lenses are replaced by a single lens when epi-illumination is used, making confocal imaging particularly applicable to incident light microscopy. We describe the results we have obtained with a confocal system in which scanning is performed by moving the light beam, rather than the stage. This system is considerably faster than the scanned stage microscope and is easy to use. We have found that confocal imaging gives greatly enhanced images of biological structures viewed with epifluorescence. The improvements are such that it is possible to optically section thick specimens with little degradation in the image quality of interior sections.
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