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Biomedical subjects

J Fowler

Publications and source records attributed to J Fowler.

At least 19 recordsLinked to original sources
PubMed1998

Relationship between potential doubling time (Tpot), labeling index and duration of DNA synthesis in 60 esophageal and 35 breast tumors: Is it worthwhile to measure Tpot?

BACKGROUND: In recent years Tpot (potential doubling time) has been measured before treatment in human tumors in an attempt to estimate the proliferation taking place during a course of irradiation. Tpot is defined as Ts/LI, where Ts is the duration of DNA synthesis and LI is the labeling index (proportion of cells synthesizing DNA). Ts is more difficult to measure than LI, so the question arises whether variation introduced during the determination of Ts is compensated by the theoretically better relevance of the quotient Tpot than of LI alone. It is not clear from comparisons with clinical outcome whether Tpot is a useful indicator of proliferation or whether LI is more prognostic, as suggested by a currently ongoing multicenter analysis elsewhere. Therefore, we investigated intercomparisons between Tpot and its components LI and Ts in two in their proliferation rates contrasting types of tumor where multiple biopsies were taken from each tumor. MATERIALS AND METHODS: Sixty patients with esophageal carcinoma and 57 patients with breast cancer were included in this study. All patients were injected with IUdR 6-8 h before surgery. From each tumor three to five biopsies were taken at surgery. Using flow cytometry, LI and Ts were measured on all biopsies in order to calculate Tpot. Logarithmic transformations of the distributions were used to examine correlations. Kappa-tests were used to assess how reliable an LI value could be in predicting the corresponding Tpot. RESULTS: Ts and LI were not completely independent, based on the within-tumor coefficients of variation (CVw). The ratio of between-tumor coefficient of variation (CVb) to the CVw suggested that the discriminative power of Tpot was higher than LI for esophagus, but the reverse in breast tumors, which had a larger range. Pearson correlation coefficients were high for log Tpot versus log LI in both types of tumor, but the predictive power was low, as shown by kappa-values of only 0.3-0.41 starting with LI and trying to predict the corresponding value of Tpot. Increasing widths of a central 'gray zone' were investigated for improved discrimination between fast and slow proliferation. Multiples of the within-tumor standard deviation, equally on each side of the median, were used to vary the width of the gray zone. Without a gray zone no more than 70% successful matching was obtained in esophagus tumors, compared with 80% in breast tumors. However, by excluding about half of the esophageal tumors an 80% success rate was achieved. In breast tumors over 90% matching was obtained more easily, keeping 80% of the tumors classifiable. For both tumor types correlations between Ts and Tpot were weak, with a trend towards short Ts associated with short Tpot and also with low LI. The latter correlation was significant for esophageal tumors and resulted in Tpot values having a smaller range than the LIs. CONCLUSION: Although there were good correlation coefficients between Tpot and LI, the predictive power of either from the other was not reliable, except by excluding a significant number of tumors close to the medians. The predictive value of LI for Tpot was higher for breast tumors because the spread in cell kinetic measurements was wide. Until more clinical data become available on outcome in comparison with LI or Tpot, it is still worthwhile to measure Tpot and to assess the prognostic value of both LI and Tpot in relation to outcome.

Adenocarcinoma↗
PubMed1998

Does sucralfate reduce the acute side-effects in head and neck cancer treated with radiotherapy? A double-blind randomized trial.

BACKGROUND AND PURPOSE: We evaluated sucralfate, well-known in the treatment of gastric ulcers, in relation to its possible reduction of radiation-induced acute complications in the treatment of head and neck cancers. MATERIALS AND METHODS: One hundred two patients were randomized in a double-blind placebo-controlled prospective setting. All patients were treated to a minimum dose of 55 Gy in 5 weeks. Oral intake of sucralfate was started at the beginning of radiotherapy and continued during the whole treatment at a dose of 1 g six times a day. All patients were scored according to a scoring system developed in our department. Weight was checked once a week. RESULTS: Comparing the time course of the mean scores for subjective intolerance, mucositis, dysphagia, dermatitis and nausea, no statistically significant differences between the two treatment arms (sucralfate, n = 38; placebo, n = 45) were observed. The mean weight loss in the sucralfate arm was 1.6 +/- 3.4 kg while it was 1.3 +/- 2.0 kg in the placebo arm. Apart from gastrointestinal upset, the administration of sucralfate did not cause any side-effects. CONCLUSION: This trial produced no clinical evidence indicating that the oral intake of sucralfate reduces the acute radiation-induced side-effects. Therefore, we do not recommend the prophylactic use of sucralfate in patients with head and neck cancer treated by radiotherapy.

Acute Disease↗
PubMed1998

Evaluating the efficacy of reflective practice within the context of clinical supervision.

This paper explores the efficacy of reflective practice within the context of clinical supervision. It examines some potential limitations that reflective practice has within the context of clinical supervision drawing upon the literature and the early stages of the author's empirical work. It concludes that whilst there is considerable congruence in the use of reflective practice within clinical supervision sessions, there are potential disadvantages in making the assumption that reflective practice should be an integral part of all forms of clinical supervision.

Education, Nursing↗
PubMed1998

Exercise groups in an insight-oriented, evening treatment program.

Exercise groups form an integral part of an insight-oriented, psychodynamic evening treatment program for a patient population characterized predominantly by mood and personality disorders. Clinical examples illustrate how the exercise groups are integrated with other therapy groups in the program. Therapists, who lead and participate in the exercise groups, attempt to maintain professional boundaries while they facilitate permissive activities where enactment of patient conflicts can occur. Events from the exercise groups frequently provide material for work in the more traditional psychodynamic groups of the program. A number of benefits of exercise groups are highlighted.

Adult↗
PubMed1998

Predictors of success in the conversion of new-onset atrial fibrillation using oral propafenone.

We have investigated the relationship of clinical variables to successful cardioversion of atrial fibrillation (AF) to sinus rhythm using an oral loading dose of propafenone. Fifty consecutive patients with recent onset (< 72 hours) atrial fibrillation of various aetiologies were included in the study cohort. All patients were given the study medication while in the emergency department and then monitored for 8 hours. All patients converting to sinus rhythm (39 out of 50, 78%) were discharged and re-evaluated at 24 hours and 30 days. We investigated the effect of clinical factors such as age, sex, presence of hypertension (HT), chronic obstructive lung disease (COPD), diabetes mellitus (DM), mitral stenosis (MS), congestive heart failure (CHF), coronary artery disease (CAD) and the duration of atrial fibrillation on conversion to sinus rhythm. Of these factors, univariate and multivariate analysis showed that only the duration of atrial fibrillation was a significant predictor of conversion (p = 0.002). Our results suggest that most patients with new-onset AF can be converted successfully to sinus rhythm with a low incidence of adverse reactions using oral propafenone in the emergency department.

Acute Disease↗
PubMed1997

Kinetics of repair in the spinal cord of the rat.

PURPOSE: Split dose experiments were carried out with two 2 Gy fractions per day at intervals ranging from 0.5 to 24 h, in order to investigate both the time to complete repair and the detailed kinetics of repair of sublethal damage in the cervical spine of rats. MATERIALS AND METHODS: Male rats of the WAG/Rij strain were irradiated at 2 Gy/min with 18 MV photons to a length of 18 mm of cervical spinal cord. Four hundred twenty-three rats were irradiated without top-up doses to investigate whether repair was complete by 24 h or whether any slow repair or proliferation occurred up to 50 days after irradiation. Three hundred seventy-nine rats were also irradiated in split dose (2 Gy + delta t + 2 Gy each day) experiments, with intervals of 0.5, 1, 2, 4, 8 and 24 h. The split dose irradiations were followed by a single top-up dose of 15 Gy (producing about half the total damage). RESULTS: Repair was complete by 24 h as the ED50 values were the same at 1, 11 and 50 day intervals for two large fractions, and for 10 fractions in 10 or 50 days. A mono-exponential component of repair of T1/2 = 0.25 (95% CI 0.16-0.48) h was determined by direct analysis using all the data and T1/2 = 0.37 (0.28-0.53) h for the split 2 Gy doses with top-up only. A bi-exponential analysis did not fit better. The presence of a second component was demonstrated graphically, with T1/2 of about 6.5 h but with a wide confidence interval from near 0 to 13 h. However, the 24 h ED50 was significantly different from all ED50s except the 8 h value. Considering all data together, an upper limit of about 7 h could be placed on any long component, or else repair could not be complete by 24 h. DISCUSSION AND CONCLUSIONS: Two components of repair (0.7 and 3.8 h) have been reported by Ang et al. (Ang, K.K., Jiang, G.L., Guttenberger, R., Thames, H.D., Stephens, L.C., Smith, C.D. and Feng, Y. Impact of spinal cord repair kinetics on the practice of altered fractionation schedules. Radiother. Oncol. 25: 287-294, 1992) in the spinal cord of Sprague-Dawley rats. Two components have also been reported by others more recently. The present results could, with its graphical interpretation, agree in principle, but with a shorter fast component and a longer slow component. A slow component of 5.5 h was reported by Ruifrok et al. (Ruifrok, A.C.C., Kleiboer, B.J. and van der Kogel, A.J. Fractionation sensitivity of rat cervical spinal cord during radiation retreatment. Radiother. Oncol. 25: 295-300, 1992) in a related strain of WAG/Rij rats. The possible presence of a slower component than Ang et al.'s 3.8 h might help to explain the four myelopathies observed in the pilot studies for the CHART clinical trial. The presence of the definite fast component (< 0.5 h) could have important consequences when pulsed brachytherapy is used to replace continuous low dose rate irradiation.

Animals↗
PubMed1997

Is pulsed dose rate more damaging to spinal cord of rats than continuous low dose rate?

BACKGROUND AND PURPOSE: Theoretical calculations suggest that pulsed dose-rate irradiation (PDR) should have approximately the same effectiveness as continuous low dose-rate (CLDR) when the same total dose is given in the same overall time, unless large doses per pulse (> 2 Gy) are used and/or non-exponential or very short half-times of repair (< 0.5 h) are present in the irradiated tissues. However, few animal experiments have been reported to test this theory, and some of them gave contradictory results. We have carried out experiments to determine whether PDR irradiation of 18 mm of cervical spinal cord in the rat was more or less effective than CLDR at 0.5-1 Gy/h, when the overall average dose rate during each day of PDR was close to the overall CLDR average dose rate. MATERIALS AND METHODS: PDR was simulated at a within-pulse dose rate of 4 Gy/h by filtered 18 MV X-rays from a linear accelerator. Two PDR schedules were used, 0.69 Gy at 1 h repetition (9 pulses per day) and 2 Gy at 3 h repetition (4 pulses per day), with overnight intervals of 16 and 15 h, respectively. The CLDR was delivered from iridium-192 wires in two concentric rings around a collar designed to fit the necks of rats so that they could eat and drink during the 72 h that was always the duration of the CLDR. Dose rate was then proportional to total CLDR dose. A range of doses was used to obtain dose response-curves, with a 15 Gy top-up dose (at 2 Gy/min, HDR) given on the day after the end of the PDR or CLDR irradiations. Animals were observed for at least 9 months to see whether fore-limb myelopathy developed. A total of 6-8 rats was irradiated per dose point, in two sets of experiments at an interval of 12 months. RESULTS: A set of 2 Gy fractions (at HDR) given daily, followed by the same top-up dose of 15 Gy at HDR, was available from a previous experiment for planning. Its ED50 was 61.2 Gy. The ED50 values found for the PDR schedules with 2 Gy at 3 h and 0.69 Gy at 1 h were 59.9 and 60.2 Gy, respectively. These were just 2% more effective than the daily HDR fractions, similar to expectations from theory if two components of repair are present. However, the CLDR irradiations resulted in no myelopathy even after doses up to 68 Gy at 0.94 Gy/h.. Thus PDR over 7 days (not at nights) appears to be more effective than CLDR over 3 days, with an effective dose-modifying factor of at least 1.1 to 1.17. DISCUSSION AND CONCLUSIONS: Reasons for this absence of effect with CLDR in these experiments are discussed, the most likely explanation being that a substantial component of repair with very short T1/2 (< 0.5 h) was present in spinal cord of these rats. There is evidence from other experiments elsewhere and in our laboratory for such a fast component of repair.

Animals↗
PubMed1997

Cabergoline treatment of acromegaly: a preliminary dose finding study.

OBJECTIVES: Studies of the dopamine agonist cabergoline in the treatment of hyperprolactinaemia have shown it to be a potent, long-acting and well-tolerated. The older dopamine agonist, bromocriptine, has traditionally had a place in the medical management of acromegaly, but poor patient tolerance of the high doses required, the need for multiple daily administration and incomplete biochemical responses have limited its role. We therefore sought to investigate the effect of cabergoline on growth hormone (GH) secretion in acromegaly and to define the most appropriate dose for suppression of GH DESIGN AND MEASUREMENTS: Patients with active acromegaly (defined as most recent random GH > 5 mU/l) were identified from the departmental clinical information system. After informed consent was obtained, basal GH levels were estimated during a 5 point day curve at least 2 months after withdrawal of any existing medical therapy for acromegaly. The cabergoline dose was escalated on a monthly basis for 4 months with a repeat 5 point GH day curve at the highest dose, and 0900 and 0930 GH estimations at the intermediate dose increment stages. Serum IGF-1 and prolactin were estimated on each occasion. Biochemical remission was defined as serum GH < 5 mU/l. PATIENTS: Eleven acromegalics were investigated. Previous treatment included surgery (7), radiotherapy (5) and bromocriptine (5). Three patients had not received any previous treatment. All had random GH persistently > 5 mU/l prior to the study. RESULTS: Ten patients completed the study. Of these, 7 showed a fall in the GH to < or = 33% and IGF-1 to < or = 67% of the basal value but only 2 achieved biochemical remission. All subjects showed maximum GH response at a dose of 0.5 mg daily of cabergoline. Four patients were unable to tolerate the maximum dose of 1 mg daily (nausea in one and nonspecific symptoms in three). The patient excluded from the analysis discontinued cabergoline and underwent surgery after 1 month because of worsening visual field defects. CONCLUSIONS: Cabergoline may be a useful adjunct to the currently available treatment for acromegaly, but rarely achieves the goal of mean GH < 5 mU/l. The maximum suppression of GH is achieved within the dose range 1 mg twice weekly to 0.5 mg daily.

Acromegaly↗
PubMed1997

The Healthcare Administrator's Associate: an experiment in distributed healthcare information systems.

The Healthcare Administrator's Associate is a collection of portable tools designed to support analysis of data retrieved via the Internet from diverse distributed healthcare information systems by means of the InfoSleuth system of distributed software agents. Development of these tools is part of an effort to enhance access to diverse and geographically distributed healthcare data in order to improve the basis upon which administrative and clinical decisions are made.

Computer Communication Networks↗
PubMed1996

How to use models of clinical supervision in practice.

It is important when considering how to implement clinical supervision to tailor the system adopted to the needs of the staff and the unit or ward. In this article, the author describes five scenarios where clinical supervision could be introduced and the best approach for each situation, using a list of six key areas.

Clinical Competence↗
PubMed1996

Combination chemotherapy with hydroxyurea, dacarbazine (DTIC), and etoposide in the treatment of uterine leiomyosarcoma: a Gynecologic Oncology Group study.

Advanced or recurrent uterine leiomyosarcomas have traditionally been resistant to most chemotherapeutic regimens. Preliminary reports suggested the combination of hydroxyurea, dacarbazine (DTIC), and etoposide (VP-16) was sufficiently effective to warrant larger trials. In a Phase II trial undertaken by the Gynecologic Oncology Group, 39 patients with advanced or recurrent leiomyosarcoma were treated with 2 g of hydroxyurea, 700 mg/m2 of DTIC, and 300 mg/m2 of VP-16 in divided doses every 4 weeks. Thirty-eight patients were evaluable for response. Two patients experienced complete responses and five had partial responses for a total objective response rate of 18.4% (95% confidence interval: 7.7-34.3%). In general, therapy was well tolerated with moderate toxicity. Six of the seven responders had disease outside the pelvis. The combination of hydroxyurea, DTIC, and VP-16 exhibits moderate activity against uterine leiomyosarcoma.

Adult↗
PubMed1996

The organization of clinical supervision within the nursing profession: a review of the literature.

There is a considerable amount of literature available on the subject of supervision within the nursing profession. However, there appears to be little structure regarding how this subject is organized within the professional literature. Thus, although the subject of supervision appears within the nursing literature as a fairly consistent theme, there has been little or no attempt by the profession to give structure to either its underpinning theory or its practice. It is apparent that the term 'supervision' within the nursing profession has different meanings for different individuals and groups. In an attempt to explore the literature relating to the United Kingdom, the author has developed a structure for the review, based upon his reading of the literature and his own experience within the profession. The review covers five areas. The first area is that of examining the need for clinical supervision within the practice of nursing. The second area of the review identifies the various ways in which the concept of supervision is used in practice, particularly identifying the variety of terminology. The third area of the review is that of the profession's perception of good practice regarding supervision. The fourth area of the review seeks to identify various models of supervision as they are used within the nursing profession. Lastly, the preparation and training for the role of supervisor is reviewed.

Clinical Nursing Research↗
PubMed1996

What is the psychiatrist's role in drugs and alcohol?

OBJECTIVE: This article describes a consensus view of the role of psychiatrists in respect of alcohol and other drug (AOD) problems, in response to the view expressed by Wodak [1]. METHOD: The data were selected on the basis of the knowledge and experience of the authors. RESULTS: Psychiatrists have made major contributions in the primary, secondary and tertiary prevention of AOD problems over many years in Australia and New Zealand. In recent years there has been an explosion of new knowledge in the AOD area and a shift from mental health to primary and public health care for these patients. Substance use disorders (SUD) are highly prevalent in all areas of psychiatric practice, requiring treatment in their own right as well as complicating the treatment of coexisting psychiatric illness. CONCLUSION: It is argued that psychiatrists have important roles in harm reduction, prevention and policy development; brief and early intervention in SUD in liaison and child psychiatry; and systematic treatment for those with dependence and other psychiatric comorbidity. A research and collaborative approach to AOD services and patients should be encouraged, rather than engaging in divisive debate over "ownership' of this area of clinical practice.

Adolescent↗
PubMed1996

Developing the security culture at the SEISMED Reference Centres.

The paper gives a brief summary of the SEISMED project and the particular role played by the Reference Centres. Details are given of the hardware and application systems in use in the Royal Hospitals (NHS) Trust (RHT), one of the SEISMED Reference Centres. It proposes, without verification, a definition of a Security Culture based on three criteria. These are suggested to be the "Awareness" the "Acceptance" and the "Actions" of the management and staff to improve Information Systems Security throughout the RHT. The way that "Awareness" was increased is shown by the specific initiatives commenced as a result of a CRAMM Risk Analysis and the management and staff training programmes. The specific initiatives mentioned include, an Information Systems Security Policy, a contingency and disaster recovery plan, improvements in the physical protection of equipment and changes to the method of access control. The "Acceptance" by the staff of these measures is considered and the success or failure of "Developing A Security Culture" examined. The role of SEISMED in this process is assessed.

Computer Security↗
PubMed1996

Development of a faculty research interest resource.

We have developed a faculty research interests resource by "mining" MEDLINE for relationships that are not directly queryable through the normal MEDLINE schema. Faculty citations are retrieved and World-Wide Web pages built to interconnect authors, their citations, and the MeSH terms that have been assigned to these citations. The design and development of the resource are discussed and examples of the results illustrated.

Databases, Factual↗