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J Fowler

Publications and source records attributed to J Fowler.

At least 37 records · Page 2Linked to original sources
PubMed2000

Structural improvement of higher education in environmental toxicology in Latin America and Europe.

Industrial development has resulted in an increased release of chemicals and other agents into the environment, resulting in damage to the environment as well as increasing the risk of adverse effects on human health. Environmental toxicology (ET) is the discipline responsible for assessing the risks to human health and the environment from the effects of new chemicals and those already present in the environment. The development of human resources in toxicology is therefore a priority in both Latin America (LA) and the European Union (EU), although LA professionals are more involved in risk evaluation than in risk assessment compared to their EU colleagues. A solid background in general toxicology will enable those interested in environmental issues to tackle local problems. Moreover, the increasing globalization of markets and, therefore, of the necessary regulations, requires harmonisation of postgraduate programmes to ensure that risk assessment and management related to the environment are dealt with uniformly and by highly qualified scientists. The Inaugural Meeting of the ALFA-OMET Toxicology', a 2-year programme supported by the European Commission, offered the opportunity to discuss a number of these issues. The present status of existing ET courses in the EU and LA and the corresponding professional profiles in the two regions were examined, and a harmonized academic curriculum for a postgraduate professional profiles in the two regions were examined, and a harmonized academic curriculum for a postgraduate course in environmental toxicology was developed. Finally, a course programme for toxicology and a specialization in environmental toxicology designed by a panel of experts was discussed, and its relevance as a model for other specialisation programmes was analysed. Exercises such as those performed by ALFA-OMET may be useful not only in promoting discussion for the implementation of national and international professional registers in LA, but also in encouraging the same, ongoing process in the EU.

Environmental Pollutants↗
PubMed2000

Improved local control for early T-stage nasopharyngeal carcinoma--a tale of two hospitals.

PURPOSE: To study the efficacy of intracavitary brachytherapy (ICT) in early T-stage nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: All early T-stage (T1 and T2 nasal cavity tumour) NPC treated with a curative intent up to 1996 were analyzed (n=743), 163 from the Prince of Wales Hospital (PWH) and 25 from Tuen Mun Hospital (TMH) were given ICT after radical external radiotherapy (ERT; group A). They were compared with 555 patients treated with ERT alone (group B). The radiotherapy techniques were identical between the two hospitals. The ERT delivered the tumoricidal dose (uncorrected biological equivalent dose (BED)-10, > or = 75 Gy) to the primary tumour, and this did not differ in technique or dosage between the two groups. The ICT delivered a dose of 18-24 Gy in three fractions over 15 days to a point 1 cm perpendicular to the midpoint of the plane of the sources. RESULTS: The local failure was significantly less (crude rates, 6.9 vs. 13.0%; 5-year actuarial rates, 5.8 vs. 11.7%) and the disease-specific mortality was significantly lower (crude rates, 13.8 vs. 18.9%; 5-year actuarial rates, 12.2 vs. 15.2%) in group A compared with group B. ICT was the only significant independent prognostic factor predictive of fewer local failures. When ICT was excluded from the Cox regression model, the total physical dose or the total BED-10 uncorrected for tumour repopulation became significant in predicting the ultimate local failure rate. The two groups were comparable in the rate of the chronic radiation complications. A significant dose-tumour-control relationship existed, plotting the local failure as a function of the total physical dose or the total BED. CONCLUSIONS: Supplementing ERT, which delivered the tumoricidal dose (uncorrected BED-10, > or = 75 Gy), with ICT significantly enhanced ultimate local control in early T-stage (T1/T2 nasal infiltration) NPC. A significant dose-tumour-control relationship exists above the conventional tumoricidal dose level.

Adult↗
PubMed2000

The potential therapeutic gain of radiation-associated gene therapy with the suicide gene cytosine deaminase.

PURPOSE: To estimate the concentration of 5-fluorocytosine (5-FC), necessary for conversion to 5-fluorouracil (5-FU) in tumours transduced with the gene cytosine deaminase (CD), to achieve clinically significant radiosensitization to radiotherapy. MATERIALS AND METHODS: Starting with a tumour control probability (TCP) of 37% from radiotherapy of 66 Gy in 2 Gy fractions, estimates were made of increase in TCP expected from sensitizer enhancement ratios (SER) of 1.1, 1.2, etc. SER values for 5-FU were obtained from a literature review. Clinical toxicity of 5-FC is also reviewed. RESULTS: 5-FU has been reported to be an effective radiosensitizer if maintained for several days after each irradiation at concentrations of 0.6-0.9 microg/ml in surrounding medium. 5-FC is well tolerated by patients at concentrations of 25-100 microg/ml (average 60 microg/ml) for 6 weeks in standard antifungal treatment. Sufficient 5-FU should be available if conversion efficiency from 5-FC is 1-3%. SER values of 1.1 to 1.2 should be achievable with daily 2 Gy fractions. In vitro and xenograft experiments are reviewed and they do not contradict the conclusions. CONCLUSIONS: Increases in tumour control of 20 to 40% can be expected, which should be detectable in a 2-arm randomized trial of 260 (for 20%) or 60 (for 40%) patients.

Animals↗
PubMed2000

The Haddon matrix: applying an epidemiologic research tool as a framework for death investigation.

The Haddon matrix is a research tool used by injury epidemiologists. Although this matrix has typically been used only in epidemiologic studies, it may serve as a framework to investigate the circumstances of traumatic deaths. This matrix consists of three rows representing time phases (before the injury incident, during the incident, and after the incident) and four columns representing the energy agent, characteristics of the deceased person, the environment, and the vehicle or vector resulting in the abnormal energy exchange, which are considered in the context of the three time phases. The authors present four cases illustrating how this epidemiologic tool can be useful during death investigations. Although the objectives for epidemiologic studies and medicolegal death investigations differ, this approach can be used to describe the circumstances surrounding an injury-related death.

Accident Prevention↗
PubMed2000

Education--who pays?

Explore the source record for details and available documents.

Education, Medical, Graduate↗
PubMed2000

Prostate cancer: epidemiology and screening.

The challenge continues-to find better methods of screening for prostate cancer, of determining who should undergo needle biopsy, and of predicting who will fail initial therapy. Investigators are looking at the value of neural networks and an array of markers to provide improved screening and prognostic information.

Journal Article↗
PubMed1999

Co-administration of gamma-vinyl GABA and cocaine: preclinical assessment of safety.

Gamma-vinyl GABA (GVG, Vigabatrin), an irreversible inhibitor of GABA transaminase (GABA-T) that inhibits cocaine-induced place preference and self administration has been proposed as a treatment for cocaine addiction. It was therefore important to assess if there was an enhanced toxicity from the combination of GVG with cocaine. No mortality was observed with administration of GVG (60 mg/kg i.v.) alone (n=8) or in combination (n=6) with cocaine (5 mg/kg i.v.). Cocaine-induced EKG alterations were not affected by GVG pretreatment. Plasma alanine amino transferase activity was reduced by GVG treatment and this was not further modified by cocaine administration. These results suggest that acute co-administration of GVG and cocaine does not result in immediate cardiovascular or hepatic toxicity of sufficient significance, to preclude further clinical trials.

4-Aminobutyrate Transaminase↗
PubMed1999

Effect of finasteride on bother and other health-related quality of life aspects associated with benign prostatic hyperplasia. PLESS Study Group. Proscar Long-term Efficacy and Safety Study.

OBJECTIVES: To investigate the long-term effects of finasteride on bother and health-related quality of life (HRQOL) in men with symptomatic benign prostatic hyperplasia. METHODS: A large prospective 4-year placebo-controlled trial (PLESS) of 3040 men with moderate to severe lower urinary tract symptoms and an enlarged prostate was performed that included self-administered questionnaires assessing HRQOL. RESULTS: Significantly greater reductions in bother score were seen for finasteride compared with placebo at every time point after 4 months. Analysis of bother scores by baseline serum prostate-specific antigen (PSA), as it is highly correlated with prostate volume, suggested greater differences from placebo for men with PSA 1.4 ng/mL or greater, primarily due to worsening after the first-year improvement in the placebo group. An activity interference domain score was significantly improved for finasteride over placebo at each time point (P<0.01), with greater treatment differences in men with higher baseline PSA levels. Comparable results were seen for worry at each time point and embarrassment due to urinary symptoms in the last 2 years of the trial. Mean changes in sexual interest and satisfaction were somewhat better for the placebo group overall, as has been previously reported, but little difference between treatments was found in sexual satisfaction measures for men with PSA 1.4 ng/mL or greater. CONCLUSIONS: Compared with placebo, men receiving finasteride had significantly less bother, activity interference, and worry due to urinary symptoms, with more pronounced differences for men with baseline PSA 1.4 ng/mL or greater. As expected, sexual satisfaction and sexual drive were slightly worse for finasteride overall, but little difference in sexual satisfaction measures was found for men with a higher baseline PSA. Thus, HRQOL was improved for finasteride compared with placebo, especially for men with a baseline PSA 1.4 ng/mL or greater.

Aged↗
PubMed1999

Must antidysrhythmic agents be given to all patients with new-onset atrial fibrillation?

We investigated the spontaneous conversion rate of new-onset atrial fibrillation (AF) in emergency department patients and the recurrence rate of AF during a 1 month follow-up period. Sixty-six consecutive hemodynamically stable patients presenting to a university hospital emergency department with new-onset atrial fibrillation (less than 72 hours duration) comprised the study population. Patients were initially monitored for 8 hours and observed for spontaneous conversion of AF to sinus rhythm. If conversion did not occur in the first 8 hours, an oral loading dose (600 mg) of propafenone was given, and patients were observed for an additional 8 hours. All patients were reevaluated at 24 hours and at 1 month. The spontaneous conversion rate in patients presenting within 6 hours of AF onset during the initial 8-hour observation period was 71%. The spontaneous conversion rate for all patients during the initial observation period was 53%. The conversion rates between patients presenting "early" (less than 6 hours) and "late" (7-72 hours) were significantly different (P < 0.001). Many patients with new-onset AF, especially those with atrial fibrillation duration less than 6 hours, may need observation only, rather than immediate intervention, to treat their dysrhythmia.

Administration, Oral↗
PubMed1999

Don't know, don't care. III.

The knowledge of and interest in Department of Defense programs to help medical students with their educational expenses in exchange for military service as a physician was studied at three medical schools representing the eastern (University of Medicine and Dentistry of New Jersey/New Jersey Medical School [UMDNJ/NJMS]), midwestern (University of Missouri at Kansas City), and western (University of Utah) United States. Despite staggering indebtedness (40% of the class of 1998 at the University of Medicine and Dentistry of New Jersey were in debt in excess of $100,000 at graduation), surprisingly few students were aware of programs such as the Health Professions Scholarship Program, the Health Professionals Loan Repayment Program, and the Specialized Training Assistance Program. Even fewer were interested when made aware of such financial assistance. Hostility to military service as a physician was common. "Patriotism" was seemingly anathema. Dwindling recruitment and retention of medical corps officers in the reserve components of our nation's armed forces is of grave concern to national security and flies in the face of medical students', hence young physicians', indebtedness for their education. Clearly Department of Defense programs must become more imaginative, certainly more financially appealing.

Adult↗
PubMed1998

Colonisation of Clostridium in the body is restricted to hypoxic and necrotic areas of tumours.

The use of gene therapy is one of the most recent molecular strategies for the treatment of cancer. It is essential, however, to have an efficient transfer system by which the desired gene can be delivered to the correct environment. The experiments described in this report investigate apathogenic Clostridium as a possible vector to transfer a specific gene product into the extracellular microenvironment of the tumour which is hypoxic/necrotic in parts, using WAG/Rij rats with transplantable rhabdomyosarcomas as a model. Our data show that Clostridium, after systemic administration of at least 10(7) spores, specifically colonises the hypoxic/necrotic areas of our tumour model, the most efficient species being C. acetobutylicum (NI-4082) and C. oncolyticum. Although spores were also detected in normal tissues for up to 4 weeks, they did not germinate in these tissues. We conclude that it seems likely that these bacteria can be used as a selective transfer system into the extracellular environment of tumours which have hypoxic regions. This strategy would be more tumour-specific than various other strategies that are currently being investigated in anti-cancer gene therapy.

Journal Article↗
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↗