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Biomedical subjects

J F Fowler

Publications and source records attributed to J F Fowler.

At least 127 records · Page 7Linked to original sources
PubMed1991

Response of the mouse mediastinum to single and fractionated X-rays.

The acute oesophageal response, after localized mediastinal irradiation in unanaesthetized mice, was assessed with a sequential, non-invasive and clinically orientated assay. Changes in body weight, after single and fractionated X-ray doses (8 fractions in 8 or 15 days and 4 fractions in 4 or 13 days), were recorded and the nadir of weight loss for each regime was used as the end-point. In our studies, quantal and non-quantal analyses of the weight loss data gave good dose-response relationships. The shapes of the dose-effect curves for single doses, 4F/4 days and 8F/8 days showed a remarkable degree of radioresistance, which became less apparent when the overall time was increased to 13 and 15 days for 4 and 8 fractions, respectively. The alpha/beta values (7-17 Gy) are within the range found for other acutely responding normal tissues. Histopathological changes were also assessed and the structural changes observed in the oesophageal epithelium, after a single dose of 34 Gy or after 46 Gy given as 3F/6 days, correlated with the gross changes observed in body weight.

Animals↗
PubMed1991

Normal tissue reactions in the British Institute of Radiology Study of 3 fractions per week versus 5 fractions per week in the treatment of carcinoma of the laryngo-pharynx by radiotherapy.

The radiobiological data obtained from a multicentre clinical trial of the British Institute of Radiology, which compared the treatment of carcinoma of the laryngo-pharynx by 3 fractions per week (3F/wk) with 5 fractions per week (5F/wk) radiotherapy, have been studied. The trial involved an intake of 734 patients between 1966 and 1975. The number of fractions, overall treatment time and total doses used by different treatment centres ranges from 9 to 40 fractions, 18 to 70 days and 3880 to 7800 cGy, respectively. An 11-13% reduction in the total radiation dose was applied for treatments with 3F/wk as compared with 5F/wk in centres treating over 6 weeks and 3 weeks, respectively. All patients were followed for 10 years from the start of treatment. Different types of early and late normal-tissue reactions were investigated, ranging from a low percentage incidence of perichondritis to 95% for slight early reactions. Greater than 80% of the late normal-tissue reactions seen were observed within the first year after the start of treatment, and 96% were observed within the first 5 years. There was no statistically significant difference in the normal-tissue event-free rates between the 3F/wk and 5F/wk treatment groups. This finding did not differ when different major treatment centres were studied separately. For a number of end-points, alpha/beta ratios and N- and T-exponents of a modified nominal standard dose (NSD) formula have been calculated.

Adult↗
PubMed1991

Physiological changes during spaceflight.

Before human beings first explored space, many dire predictions from the scientific community suggested that weightlessness was not compatible with life. Although these prophesies have been proven false, many physiological alterations do occur in microgravity conditions. Other systems are altered as well, but the cardiovascular, musculoskeletal, and immune systems undergo adaptations that may pose problems for the space traveler, especially on returning to gravity.

Adaptation, Physiological↗
PubMed1990

How worthwhile are short schedules in radiotherapy? A series of exploratory calculations.

A series of calculations is presented of log cell kill for most of the fractionated schedules that could conceivably be devised using 1, 2 or 3 fractions per day and 3, 5 or 7 treatment days per week, in overall times of 1 to 7 weeks inclusive. The basic assumption is that late reactions are kept constant, and that repair of sublethal damage is complete, i.e. intervals are at least 6 h. A wide range of effective doubling times of tumor cells is assumed: 2, 3, 5, 7, 10, 20 days and infinity. The results show that optimum overall times depend primarily on (1) the doubling time for cells in the tumor and (2) the intrinsic radiosensitivity alpha (which is proportional to alpha/beta in one of the assumptions made here). Optimum overall times are proportional to (1) but can increase even more steeply with increasing radiosensitivity or alpha/beta. Short overall times are required for tumors with low alpha/beta and/or fast proliferation. Optimum overall times are, interestingly, relatively independent of the number and frequency of fractions. However, therapeutic ratios are higher if larger numbers of smaller fractions are used within the selected overall time. This is a critical factor in achieving adequate tumor cell kill. For median potential doubling times of 5 days, and median radiosensitivity, overall times of 2.5 to 4 weeks would be optimal. More slowly proliferating tumors, possibly about half of many types of carcinoma, should be treated with longer overall times, but selection is necessary. Doubling or halving the cell doubling time would mean 5-8 or 1.2-2 weeks overall time, respectively. Similarly, for a 5 day doubling time, a tumor with alpha/beta = 5 Gy should be treated in less than a week; but if alpha/beta = 20 Gy the optimum overall time could exceed 7 or 8 weeks. A tumor with cells that double in 3 days would require overall times of 0.3, 2.5 and 6.5 weeks for alpha/beta values of 5, 10 and 20 Gy, respectively. Acute effects (excluded in the analysis) would disqualify some of the shorter schedules. We can hope to know potential doubling times (from flow cytometry) and eventually values of alpha (and alpha/beta). It is important that assays of both should continue to be developed. When such individual values are available, optimum overall times can be chosen, as described here, within which the maximum practicable number of small fractions can be given.(ABSTRACT TRUNCATED AT 400 WORDS)

Cell Survival↗
PubMed1990

Further analysis of the time factor in squamous cell carcinoma of the tonsillar region.

Recently, Bataini et al. reported that overall time was the major treatment-related determinant of local control in 465 squamous carcinomas of the tonsillar region. They did not, however, quantify the relationship or relate it to the doubling time of tumorigenic cells, except qualitatively. This note reports an attempt at that quantification.

Carcinoma, Squamous Cell↗
PubMed1990

Simultaneous contact allergy to neomycin, bacitracin, and polymyxin.

Simultaneous contact allergy to neomycin, bacitracin, and polymyxin was seen in two patients. Although neomycin sensitivity is common, bacitracin and polymyxin are less frequently considered as causes of allergic contact dermatitis. Allergy to all three items simultaneously has not been previously reported.

Adult↗
PubMed1990

Radiobiological aspects of low dose rates in radioimmunotherapy.

It is assumed that initial dose rates of 10-20 cGy/hour and total doses of 1500-2000 cGy, delivered with effective half-lives of a few days, are reasonable starting points for assessing the radiobiological effects of such low and declining dose rates. Such doses might kill 2 or 3 logs of cells out of the 9 or 10 required for tumor eradication; this is well known. The emphasis in this paper is on the change of effectiveness (per Gy) with change in dose rate. Biological effectiveness, in terms of log cell kill per Gy, will be less than that of higher dose rates because there is more time for repair of sublethal radiation injury. This loss in Relative Effectiveness, RE, is unlikely to exceed 20% in most types of tumor cell, compared with conventional external beam radiation schedules. Therefore, a tumor or metastatic deposit that would require 60-70 Gy to sterilize it using conventional radiotherapy with 2 Gy fractions (or traditional radioactive implants at 50 cGy/hr) would require 70-84 Gy at the lower dose rates available from radioimmunotherapy. This is the major dose rate effect and so far we have ignored proliferation. In the dose-rate range of 10-300 cGy/hr in vitro, highly variable depending on type of cell, division might be prevented but not progression through the cell cycle. Additional cell kill is observed because cells accumulate in the radiosensitive G2 phase; this is the inverse dose-rate effect. However, that range of dose rates comes from in vitro experiments where cells are doubling in number every 0.5 to 1 day. In vivo they double more slowly so it is possible that the unpredictable benefit of G2 accumulation, or partial synchrony, could occur at lower dose rates than 10 cGy/hr in human tumors. The dose rates necessary to kill cells at exactly the rate they are proliferating (which of course would not alone eradicate tumors or metastases) can be calculated, if values are assumed for intrinsic radiosensitivity and doubling rate of cells. In median ranges, dose rates of 2-3 cGy/hr should just counteract proliferation. Higher dose rates, maintained for a few days, could cause 2 or 3 logs of cell kill which would be observed as partial regression, as has been reported clinically and in animal experiments.

Antibodies↗
PubMed1990

90Y.B72.3 against pancreatic cancer: dosimetric and biological analysis.

Nude mice xenografted with a human pancreatic carcinoma cell line were injected with yttrium-90 (90Y) conjugated to diethylene triaminepenta acetic acid (DTPA) alone, and DTPA covalently linked to a monoclonal antibody, B72.3. The animals were sacrificed in temporal sequence to evaluate isotope distribution. Dosimetry was carried out using the principles outlined in MIRD and ICRU Report 32. Results are expressed as percent uptake per unit mass in organs and tumor and as relative absorbed dose normalized to 90Y uptake in liver at 7 hr. When conjugated to B72.3, an 8-fold increase in isotope localization in the tumor was noted by 24 hr. When the relative absorbed dose is calculated for 90Y and 90Y.B72.3, a 26-fold increase in tumor dose is noted for the 90Y conjugate. Normal tissues show no to modest (less than 5x) enhanced dose with 90Y.B72.3. B72.3, therefore, deserves further investigation as a potential monoclonal antibody for targeting therapeutic radioisotopes and possibly diagnostic radioisotopes to pancreatic cancer. Radiobiological aspects of the low dose rates from radioimmunotherapy are discussed.

Animals↗
PubMed1990

Recruitment, follow-up and analysis times in clinical trials of cancer treatment: a case study.

A study has been made of the way in which the number of events available for analysis in a clinical trial was dependent on the recruitment period, the maximum follow-up time on individual patients and the length of time between the start of the trial and its analysis. The events considered were deaths, local recurrences and late radiation effects on normal tissue in patients treated for cancer of the laryngo-pharynx by two different fractionation regimes. The relationship is demonstrated between the number of events and the 95% confidence intervals that can be placed on differences between results in the two arms of the trial. It was found, in this particular trial, that no significant improvement in precision was gained by following up patients beyond 5 years or carrying out the analysis later than 2 years after the end of recruitment. The results are discussed in the context of the initial design of clinical trials, particularly those in which the aim is to test therapeutic equivalence.

Clinical Trials as Topic↗
PubMed1990

Dosimetric intercomparison in the British Institute of Radiology fractionation study of 3F/week versus 5F/week in radiotherapy of laryngo-pharynx cancer.

A dose intercomparison was carried out by the National Physical Laboratory between the seven radiotherapy centres which contributed the largest number of patients to the British Institute of Radiology fractionation study of three fractions per week versus five fractions per week in clinical cancer treatment. Six of the centres showed remarkable agreement within the acceptable limits of error of the measurements. In one centre there appeared to be a physical dose discrepancy of 2.8% which was materially less than could be detected clinically.

Humans↗
PubMed1990

Final report of the general clinical results of the British Institute of Radiology fractionation study of 3F/wk versus 5F/wk in radiotherapy of carcinoma of the laryngo-pharynx.

The 10 year follow-up of a clinical trial involving the comparison of 3F/wk versus 5F/wk in radiotherapy of squamous cell carcinoma of the larynx and hypopharynx has now been completed. The trial involved an intake of 734 patients between 1966 and 1975. The classification of all patients has been revised to conform with the latest TNM publication. A reduction in total dose was made for 3F/wk compared with 5F/wk. This varied between 13% and 11% in centres treating over 3 weeks and 6 weeks, respectively. No statistically significant differences have been found between the two arms (3F/wk versus 5F/wk) of the trial in any of the main group analyses. A number of sub-group analyses relating to survival, tumour-free and laryngectomy-free rates and to the comparison of acute or late normal-tissue radiation damage have also been performed. No differences have been found that could be considered to be statistically significant in relation to the particular sub-group. Previous interim reports suggested minor differences in sub-group analyses between the 3F/wk and 5F/wk regimes in this trial; these have diminished now that the full follow-up data are available. This trial has provided evidence on which clinicians may base their choice between either a 3F/wk fractionation regime or a conventional 5F/wk treatment protocol in the treatment of carcinoma of the laryngo-pharynx.

Carcinoma, Squamous Cell↗
PubMed1990

The predictive value of tumor classification compared with results of the British Institute of Radiology fractionation trial in the treatment of laryngopharyngeal carcinoma.

Data from a clinical trial involving 734 patients have shown the value and the deficiencies of the current Union Internationale Contre le Cancer's tumor, node, and metastasis classification system for prognostic purposes. The tumor-category classification provides a good discriminant for both nodal involvement and survival; however, the previous node classification system only discriminated between node-negative and node-positive patients, as nodal fixity was not found to be a discriminator. The current anatomical site classification is ambiguous for some laryngeal and pharyngeal subsites, and modifications to the present system based on prognostic values are proposed. A difference in patient age between tumor categories has been shown, and various differences in incidence and survival data for the sexes have been demonstrated. Differences in observed and expected survival rates are related to continued late deaths from tumor. Multivariate analyses have shown that stage grouping is the most powerful prognostic discriminator, followed by anatomical site and age.

Adult↗
PubMed1990

Immediate contact hypersensitivity to acrylic acid.

A chemical worker developed acute generalized urticaria after working with acrylate compounds in a laboratory. Immediate-hypersensitivity testing to acrylic acid yielded a severe local reaction. Testing with other acrylate compounds was negative. Re-exposure in the work-place to vapors of acrylic acid resulted in generalized urticaria. With the cooperation of the employer, the patient moved to a marketing job with no contact with acrylic acid and has remained free of urticaria since.

Acrylates↗
PubMed1990

HLA antigens in lichen sclerosus et atrophicus.

Several reports have found conflicting data regarding the association between lichen sclerosus et atrophicus (LSA) and HLA types. Association with HLA-A31 and -B40 has been noted, whereas another report found no correlation. We are the first to specifically examine HLA types in white patients in the United States. We have found a significant association between LSA and HLA-A29 and -B44 individually and an even stronger association with the combination of A29 and B44. A review of previous LSA-HLA studies, as well as several reports of HLA typing in familial LSA, is discussed, with consideration given to possible reasons for the discrepancies among the various studies.

Adolescent↗
PubMed1990

Hot tub (Pseudomonas) folliculitis.

Folliculitis caused by Pseudomonas aeruginosa is a rare, adverse effect of the therapeutic or recreational use of hot tubs, whirlpools, and occasionally swimming pools. The condition is characterized by painful, papulopustular skin lesions often accompanied by low-grade fever, malaise, and other systemic symptoms. Prompt recognition and treatment may shorten the duration of the disease and, more importantly, prevent further cases by identifying the source of exposure.

Adult↗