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Biomedical subjects

J M Fitzpatrick

Publications and source records attributed to J M Fitzpatrick.

At least 55 records · Page 3Linked to original sources
PubMed1999

Future prospects in prostate cancer.

BACKGROUND: Prostate cancer has displayed an increase in incidence unparalleled by any other tumor in the last two decades, with a steady, more gradual increase in mortality rate. Current curative strategies are focused on the detection and treatment of early-stage (T1-2 N0 M0), clinically significant tumors. METHODS: To this aim, refinement of surgical approaches, with appropriate adjuvant therapies, will ensure more complete cancer control, while minimizing associated morbidity. New delivery systems for radiotherapy, as well as other energy sources, are evolving, while a number of promising pharmacological agents, including angiogenesis inhibitors and drugs which alter signal transduction pathways, are currently under investigation. Early detection is also being facilitated by a more widespread implementation of screening programs. Advances in tumor markers, and imaging and biopsy techniques, will allow more accurate preoperative staging. These, coupled with improvements in prognostic markers, aid the physician and patient alike in deciding on the suitability of treatment options with better estimation of outcome. Perhaps the most exciting developments in prostate cancer will come from knowledge of the molecular mechanisms underlying carcinogenesis. The potential for the development of diagnostic and therapeutic tools is immense. The efficacy of treatment can be studied at a molecular level, and strategies for preventing or slowing the development of malignancy can be formulated. RESULTS AND CONCLUSIONS Application of this knowledge in the form of gene and cellular therapy and in the development of novel systemic agents is beginning to enter the realm of clinical practice, and it may be in this field that means for cure and prevention of prostate cancer will eventually be found.

Clinical Trials as Topic↗
PubMed1999

Regulation of Fas antibody induced neutrophil apoptosis is both caspase and mitochondrial dependent.

Resolution of neutrophil mediated inflammation is achieved, in part, through induction of neutrophil apoptosis. This constitutively expressed programme can be delayed by inflammatory mediators and induced by ligation of the Fas receptor. However, functional activation of the neutrophil results in resistance to Fas signalled death. We evaluated the effects of Fas antibody engagement on caspase activation and mitochondrial permeability, and the impact of co-stimulation by lipopolysaccharide (LPS) or granulocyte macrophage-colony stimulating factor (GM-CSF) on these events. Fas engagement by an agonistic anti-Fas antibody resulted in enhanced caspase 3 and 8 activity and increased mitochondrial permeability. Studies with pharmacological inhibitors of caspase activity showed that activation of caspase 8 occurred before, and activation of caspase 3 occurred after mitochondrial disruption. The mitochondrial stabilising agent bongkrekic acid also inhibited caspase activation and apoptosis. LPS, GM-CSF and increased glutathione stabilised the mitochondria and inhibited caspase 3. Caspase 8 activity was also inhibited by co-stimulation through a mechanism independent of mitochondrial stabilisation. Glutathione directly inhibited caspase 3 and 8 activity. We conclude inhibition of Fas antibody induced apoptosis by inflammatory proteins is associated with augmented mitochondrial stability and reduced caspase 3 activity that may be glutathione mediated.

Acetylcysteine↗
PubMed1999

High intensity focused ultrasound in benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is an extremely common condition and represents a major health issue in terms of patient numbers and treatment cost. Traditionally, the choice of treatment has been between watchful waiting and surgery, however, the side effects of surgery lead to reluctance for treatment in many men, other than those with severe symptoms and complications. In the last 2 decades there has been a rapid expansion in the number of treatments being offered and the number of patients submitting to novel therapies. Medical management has evolved to achieve a central role in the management of BPH. Heat based treatments are also being investigated with considerable interest. Transrectal high intensity focused ultrasound (HIFU) is one such treatment, which allows radiation-free treatment, without the need for intra-urethral manipulation. Imaging can be performed during treatment and treatment results in symptomatic improvement, which is retained with medium-term follow-up. It involves a brief hospital stay and post-operative complications are few. The use of HIFU has also been extended to the treatment of renal, prostatic and bladder tumours and the results in these areas suggest further expansion of its role in urological practice.

Follow-Up Studies↗
PubMed1999

Plasma concentrations of glutathione S-transferase isoenzyme are raised in patients with intestinal ischaemia.

BACKGROUND: The mortality rate associated with acute mesenteric ischaemia (AMI) remains high. Diagnosis is frequently confounded by the non-specific history and physical signs, in conjunction with the absence of a reliable biological assay. Glutathione S-transferase (GST) is an enzyme with a crucial role in cellular homoeostasis, the alpha isoenzyme of which is highly specific to small bowel and liver. This study assessed alphaGST as a marker for AMI. METHODS: Twenty-six patients with acute abdominal pain were enrolled. Each patient manifested a diagnostic dilemma, with a potential diagnosis of AMI. Plasma was reserved for alphaGST assay during routine blood testing and stored at -20 degrees C for analysis. A final diagnosis was made by autopsy, laparotomy, a definitive other investigation or a return to full health. RESULTS: Twelve patients had AMI. Plasma alphaGST was significantly increased in patients with AMI (P < 0.0001). Although pH differed and other biochemical changes occurred, only alphaGST accurately predicted AMI. CONCLUSION: A threshold of 4 ng/ml for alphaGST was 100 per cent sensitive and 86 per cent specific for AMI. If these observations can be confirmed, evaluation of alphaGST may reliably predict the presence or absence of AMI.

Abdomen, Acute↗
PubMed1999

Shift work and its impact upon nurse performance: current knowledge and research issues.

Previous research investigating shift work and its impact upon the quality of registered nurse performance and outcomes (including biological, psychosocial and organizational) is reviewed. The present study, which involved non-participant observation of staff nurses (n = 34) within their first year of practice (Part 1 or Part 12 of the United Kingdom Professional Register), is described. The findings demonstrated support for earlier research which suggested that 12 1/2 hour shifts are associated with less effective performance. This study, together with previous research, highlights important indicators for the design and management of future empirical work which is required to investigate the influence of shift work upon process as well as outcomes for nurses, service users and the employing organization. This is particularly pertinent in the light of recent changes in work patterns. The well-being and effectiveness of the nursing workforce requires enhancement, and the effective management of shift-work is a key strategy in achieving this.

Employee Performance Appraisal↗
PubMed1999

Retrospective intermodality registration techniques for images of the head: surface-based versus volume-based.

The primary objective of this study is to perform a blinded evaluation of two groups of retrospective image registration techniques, using as a gold standard a prospective marker-based registration method, and to compare the performance of one group with the other. These techniques have already been evaluated individually [27]. In this paper, however, we find that by grouping the techniques as volume based or surface based, we can make some interesting conclusions which were not visible in the earlier study. In order to ensure blindness, all retrospective registrations were performed by participants who had no knowledge of the gold-standard results until after their results had been submitted. Image volumes of three modalities: X-ray computed tomography (CT), magnetic resonance (MR), and positron emission tomography (PET) were obtained from patients undergoing neurosurgery at Vanderbilt University Medical Center on whom bone-implanted fiducial markers were mounted. These volumes had all traces of the markers removed and were provided via the Internet to project collaborators outside Vanderbilt, who then performed retrospective registrations on the volumes, calculating transformations from CT to MR and/or from PET to MR. These investigators communicated their transformations, again via the Internet, to Vanderbilt, where the accuracy of each registration was evaluated. In this evaluation, the accuracy is measured at multiple volumes of interest (VOI's). Our results indicate that the volume-based techniques in this study tended to give substantially more accurate and reliable results than the surface-based ones for the CT-to-MR registration tasks, and slightly more accurate results for the PET-to-MR tasks. Analysis of these results revealed that the rotational component of error was more pronounced for the surface-based group. It was also apparent that all of the registration techniques we examined have the potential to produce satisfactory results much of the time, but that visual inspection is necessary to guard against large errors.

Algorithms↗
PubMed1998

Mucosal metabolism in ulcerative colitis and Crohn's disease.

PURPOSE: Colonic mucosal metabolism of butyrate may be impaired in ulcerative colitis. In this study we sought to confirm this observation, to determine if a similar change occurs in Crohn's colitis, and to establish whether a panenteric disorder of butyrate metabolism exists in either condition. METHODS: With use of a microculture technique, mucosal metabolic fluxes of 14[C]-labeled butyrate and 14[C]-labeled glutamine were measured as 14[C] carbon dioxide production in mucosal biopsy specimens from the colon and ileum in patients with ulcerative colitis, Crohn's colitis, and healthy bowel. Results were expressed as pmol/microg biopsy DNA/hour. RESULTS: In the colon the mucosal metabolic fluxes of both butyrate and glutamine are reduced in both ulcerative colitis and Crohn's colitis compared with healthy controls. These changes were most marked in the presence of moderate to severe mucosal inflammation, there being no significant difference in mucosal metabolic flux between mildly inflamed mucosa and healthy controls. In the ileum the mucosal metabolic fluxes of butyrate and glutamine did not differ between healthy controls and those with either ulcerative colitis or Crohn's colitis. CONCLUSIONS: Changes in colonic mucosal metabolism of butyrate and glutamine in inflammatory bowel disease occur as a consequence of the inflammatory process and are not peculiar to ulcerative colitis. Ileal mucosal metabolism is unchanged in ulcerative colitis and Crohn's colitis, indicating the absence of a panenteric abnormality of mucosal metabolism in these two conditions.

Biopsy↗
PubMed1998

Changes in regional renal blood flow after unilateral nephrectomy using the techniques of autoradiography and microautoradiography.

PURPOSE: To determine alterations in regional renal blood flow following unilateral nephrectomy using an autoradiographic technique. The role of prostaglandins and the sympathetic nervous system in the mediation of these changes was assessed. MATERIALS AND METHODS: C-14 iodoantipyrine was used as a tracer to measure intrarenal blood flow in anaesthetised rats at multiple time points following nephrectomy. Autoradiographs were produced from tissue sections. C-14 concentrations were measured from standards thus allowing blood flow values to be calculated. RESULTS: Base line values for cortical and medullary blood flow were 806 +/- 63 and 373 +/- 39 ml./100 gm./min. (mean +/- SEM) respectively. At 2 hours post nephrectomy blood flow to both the cortex and medulla increased significantly (1152 +/- 54 and 594 +/- 37; p < 0.05). Blood flow had returned to control levels by 24 hours and was maintained at 5 days post-nephrectomy. Multiple discrete regions of high blood flow within the cortex were observed. Microautoradiography defined the morphological location of these discrete regions of higher blood flow as periglomerular vasculature. Diclofenac administration did not inhibit the augmentation in cortical blood flow post-nephrectomy, while medullary blood flow fell below base line values at both 30 minutes and 2 hours following nephrectomy. Sympathetic denervation did not affect the changes in cortical blood flow seen following nephrectomy, but did ameliorate the changes in medullary blood flow. CONCLUSIONS: Significant, transient changes in regional renal blood flow occur in the residual kidney following unilateral nephrectomy. The interaction between vasoactive mediators and the autonomic nervous system which produces changes in cortical blood flow is complex. It is evident, however, that medullary blood flow is dependent on local prostaglandin production and is also influenced by sympathetic nervous supply.

Animals↗
PubMed1998

Sublabial, transseptal, transsphenoidal approach to the pituitary region guided by the ACUSTAR I system.

OBJECTIVE: Advances in imaging resolution have resulted in superior visualization of intracranial anatomy. Because of the inherent complexity of the surgical exposure of these lesions, intraoperative localizing techniques are required. Currently, C-arm fluoroscopy provides only two-dimensional localization for these anatomic structures. The recently described ACUSTAR I system, developed in conjunction with Codman and Shurtleff, Inc. (Randolph, Mass.), is an interactive, image-guided device that allows three-dimensional localization with a degree of accuracy previously unattainable. We assessed the clinical utility of the ACUSTAR I system for intraoperative spatial confirmation during transsphenoidal approaches to pituitary lesions. METHODS: Eight patients underwent transsphenoidal approaches to pituitary lesions with the assistance of the ACUSTAR I system. The spatial relationships were clinically judged intraoperatively by the surgeon and by use of traditional C-arm fluoroscopy and then were compared with the ACUSTAR I system results. RESULTS: In all eight patients, the ACUSTAR I system correctly displayed the surgical orientation and provided localization to within less than 1 mm. In two patients, this facilitated the redirection of an errant approach. No complications were associated with the use of this image-guided device. CONCLUSIONS: The ACUSTAR I system is useful in displaying accurate, three-dimensional anatomic relationships during transsphenoidal approaches to pituitary lesions. This system provides critical information intraoperatively to redirect errant approaches and prevent significant morbidity.

Adenoma↗
PubMed1998

An exploratory study of similarities and differences between senior students from different pre-registration nurse education courses.

A triangulation design using two simulations, non-participant observation and a semi-structured interview to explore senior student nurse performance in South East England is described. A comparison of student nurse performance (registered general nurse [RGN] programme n = 34; registered nurse Project 2000 diploma programme n = 34; integrated degree programme n = 31) indicated many similarities but also some important differences in outcomes which included: a more systematic approach to information-seeking, better care-planning skills and higher quality nurse performance among integrated degree programme participants; use of a model and the immediate role of the nurse to guide information-seeking and better care-planning skills and weaknesses in clinical nurse performance among RGN programme participants; and weaknesses in the information-seeking, care-planning and clinical nurse performance among Project 2000 diploma participants. There were no significant differences between the clinical performance scores of the RGN and diploma programme participants. The interview data suggested that the integrated degree programme participants had a client focus in contrast to the professional focus of RGN and Project 2000 diploma participants. The findings, however, must be viewed within the context of an exploratory study of limited sample size. The research was funded by the English National Board for Nursing, Midwifery and Health Visiting.

Adult↗
PubMed1998

Metabolic substrate utilization differs in ileal faecal and urinary reservoirs.

BACKGROUND: Construction of an ileal faecal or urinary reservoir profoundly alters ileal luminal ecology and availability of mucosal metabolic substrates. The aims of this study were to measure mucosal metabolic flux of butyrate and glutamine in histologically normal (control) ileum and to determine the effect of reservoir construction on metabolic fluxes in patients with ileal pouch-anal anastomosis and ileocystoplasty. METHODS: Endoscopic biopsy samples were obtained from normal ileum (n = 10), ileum of patients with ulcerative colitis (n = 10), ileal pouch-anal anastomosis (n = 7), ileocystoplasty (n = 7) and ileal conduit (n = 7). Using a closed microculture technique, biopsy utilization of 14C-labelled butyrate and glutamine was measured as [14C]carbon dioxide production. Biopsy DNA content was measured and [14C]carbon dioxide evolution expressed as picomoles [14C]carbon dioxide per microgram DNA per hour. RESULTS: The metabolic flux of both butyrate and glutamine was reduced in ileal pouch mucosa compared with that of ileal mucosa in patients with ulcerative colitis. In contrast, the metabolic flux of buyrate alone was reduced in ileal mucosa from ileocystoplasty and ileal conduit compared with that in normal ileal mucosa, while the metabolic flux of glutamine remained unchanged. CONCLUSION: Ileal mucosal metabolic fluxes measured in vitro are altered by changing luminal ecology in vivo. These changes may affect the health and mucosal integrity of ileum used to construct these reservoirs.

Butyrates↗
PubMed1998

Prostate cancer: how aware is the public?

OBJECTIVE: To assess the public awareness of prostate cancer and willingness to seek medical attention for urinary symptoms, and to determine associated factors. SUBJECTS AND METHODS: A community survey was conducted using a questionnaire administered by the interviewer to 280 randomly selected Irish men aged 40-69 years. RESULTS: A quarter of the men had not heard of prostate cancer; factors associated with having heard were nonmanual social class, living with a female partner and a history of treatment for urinary disease. Eighty per cent said they would be willing to attend a GP if they had urinary symptoms; associated factors were living with a female partner, having heard of prostate cancer and having seen a GP more than once in the preceding year. Just over half deemed attendance to be urgent/important; associated factors were having heard of prostate cancer, living with a female partner and having a relative with cancer. Having a General Medical Services card (a means-tested medical card entitling the holder to free medical services) was negatively associated. Lower social class was negatively associated with routine questioning by a GP about urinary symptoms. CONCLUSIONS: There is a marked social-class gradient in knowledge and willingness to seek medical advice. In the absence of population screening, earlier clinical presentation with prostate cancer is essential if prognosis is to be improved; there is an evident need to improve prostate cancer awareness, particularly in the lower social classes, if this goal is to be achieved.

Adult↗