Biomedical subjects
Publications and source records attributed to J F Fowler.
Allergic contact dermatitis to gold is very rarely reported. The occurrence of 2 recent cases in our department prompted a review of the literature, especially regarding the optimal reagents for patch testing. Gold chloride is most commonly used but may cause persistent dermatitis at the test site. Gold sodium thiosulfate is commercially available in petrolatum and is a reliable, non-irritant preparation for patch testing.
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The lungs of mice were irradiated with 1, 4, or 7 fractions of X rays or neon ions in a 4-cm spread Bragg peak. Lung function as a function of total radiation dose was tested at 7 and 12 months after irradiation by measuring the resting breathing rate in a whole-body plethysmograph. The isoeffect doses increased sequentially with X rays for 1 through 4 to 7 fractions, demonstrating repair of sublethal radiation injury as previously reported. There was also a significant increase of isoeffect dose with neon ions between 1 and 4 fractions but no further increase at 7 fractions. Thus repair instead of potentiation of radiation injury in lung clearly occurred after neon ion irradiation. The effectiveness of neon ions appeared to be closer to that of neutrons with a mean energy of 8 meV than those with a mean energy of 2.3 meV.
Rapid proliferation of malignant cells has not previously been emphasized as a major source of failure to control tumors. Evidence is presented that the effective doubling times of clonogenic cells in human tumors during multifraction radiotherapy are in the range of a few days, that is, similar to the pre-treatment Potential Doubling Times and much shorter than Volume Doubling Times. Evidence from animal tumor studies leads to the same conclusion. Accelerated fractionation should be considered for individual human tumors whose LI is measured (e.g., by flow cytometry and the BUdR antibody) and found to be too high.
Subacute cutaneous lupus erythematosus has been clearly recognized as a distinct cutaneous manifestation of lupus erythematosus. Two forms have been described, an annular erythema and a papulosquamous variant. Previous data have suggested that these patients have a high incidence of mild to moderate systemic disease, anti-Ro (SS-A) antibodies, and human lymphocyte antigen (HLA)-DR3, particularly the annular form. We studied forty-nine patients with subacute cutaneous lupus erythematosus seen in local private practices in our area. Lesions of chronic cutaneous lupus erythematosus were seen in 34.8% of our patients. Twenty-five patients (51%) fulfilled the American Rheumatism Association criteria for the classification of systemic lupus erythematosus, and renal disease was present in nine of these patients (including 3 with decreased function). Antibodies to Ro (SS-A) and/or La (SS-B) were present in only sixteen patients, and HLA-DR3 was found in only seventeen patients. Twenty-two patients had inactive cutaneous disease at follow-up. We concluded that our patient population with subacute cutaneous lupus erythematosus skin lesions is less distinctive than previous literature suggests. The serologic and immunogenetic correlates were not demonstrated. The full range of lupus erythematosus-related disease was seen, although most patients follow a benign course.
The time required between well-separated pairs of doses of X-rays (e.g. 2F/day) for repairable damage to be apparently completed increases with dose per fraction and with the alpha/beta ratio, even when the underlying half-life is invariant.
The radiosensitization of Chinese hamster V79 cells in vitro by air and misonidazole at low X-ray doses (0.2-6.0 Gy) had been studied. These survival data, together with high-dose data, were fitted to the linear quadratic model ln S = -(alpha D + beta D2), deriving estimates of alpha and beta by six different methods to illustrate the influence of the statistical treatment on the values so derived. This in vitro study clearly demonstrated that the survival parameters alpha and beta are dependent to some degree on the method of analysis of the raw survival data; however, their ratios, the values of oxygen enhancement ratios (OERs) and radiosensitizer enhancement ratios (SERs) derived from the different methods, are similar. All methods of analysis give reduced OERs at low radiation doses for combined low- and high-dose X-ray data. However, the OERs are still appreciably high, ranging from 2.45 to 2.50 for an oxic dose of 2 Gy. All methods of analysis gave reduced SERs at low doses for combined low and high X-ray dose data for hypoxic cells irradiated in 1 mmol dm-3 misonidazole. At survival levels corresponding to doses of 2 Gy in the presence of 1 mmol dm-3 misonidazole and SERs ranged from 1.2 to 1.5.
Urticaria pigmentosa, characterized by cutaneous mast cell proliferation, usually occurs sporadically in childhood and resolves over a period. Rarely is the condition seen in two or more members of a family. We encountered a family in which urticaria pigmentosa occurred in four members of two generations. Skin findings were similar in all four. No systemic manifestations other than occasional flushing episodes were noted in any of the affected individuals. HLA typing was performed, but no significant correlation between affected and unaffected individuals was seen. In a review of a number of previously reported cases, we found a slight female preponderance.
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Neonatal lupus erythematosus (LE) is a syndrome that is manifested by LE skin lesions and/or congenital heart block, occurring in infants at, or shortly after, birth. The syndrome is believed to be caused by transplacental passage of an IgG antibody, usually the anti-Ro (SS-A) antibody, from the mother to the infant. Although the mother may have a connective tissue disease or may be healthy, the common characteristic is the presence of maternal circulating anti-Ro antibody. It has been believed that the HLA determinants demonstrated in children who have neonatal LE were not a factor in the expression of the syndrome. We report the occurrence of neonatal LE, manifested by photosensitivity and discoid LE skin lesions, in one fraternal twin. HLA studies of this affected twin demonstrated the presence of DR3. Anti-Ro antibody was present in the mother, but was not present in either child at 4 months post-delivery. HLA determinants may be involved in the expression of disease in neonates who have been exposed to the anti-Ro antibody. Furthermore, the presence of circulating antibodies in the unaffected twin causes us to question the assumption that the anti-Ro antibody is the causative factor for the occurrence of tissue injury in children with neonatal LE.
In this review the poor clinical gains from hyperbaric oxygen (HBO) and misonidazole (MISO) are discussed critically. The biggest factor reducing clinical gains is almost certainly reoxygenation. Other possible reasons include vasoconstrictive self-limitation of HBO and neurotoxicity of MISO, so that the radiosensitization of any hypoxic cells in human tumors was not adequate. Nevertheless, there have been some positive clinical results, so that hypoxic cells can sometimes be a problem in some tumors, especially those of the head and neck, even after multiple fraction radiotherapy. While hypoxic cell radioresistance is obviously only one form of radioresistance it is a large factor of resistance when hypoxic cells are present. Current developments are briefly reviewed: the 'new' clinical sensitizers Ro-03-8799 and SR-2508 which should be 3 to 10 times more efficient than MISO if viable hypoxic cells are present; and methods of measuring which human tumors might have significant numbers of hypoxic viable cells.
Clinical interest in the use of more and smaller dose fractions in radical radiotherapy has been stimulated by recent reviews of experimental results with normal tissues. It has been found that if the dose per fraction is reduced (i.e., in hyperfractionation) there is sparing of late responding normal tissues relative to those which respond early. This phenomenon can be understood in terms of the shapes of the underlying dose effect relationships, which can be described using the linear quadratic equation. The ratio (alpha/beta) of the linear (alpha) and quadratic (beta) terms is a useful measure of the curviness of such dose effect curves. Low alpha/beta values (1.5 to 5 Gy) have been observed for late responding normal tissues and indicate that radiation damage should be greatly spared by the use of dose fractions smaller than the 2 Gy used in conventional radiotherapy. By contrast the high alpha/beta values (6-14 Gy) observed for acutely responding normal tissues indicate that the response is relatively linear over the dose range of clinical interest. Hence less extra sparing effect is to be expected if lower doses per fraction are administered. If tumors respond in the same way as acutely responding normal tissues then hyperfractionation might confer a therapeutic gain relative to late responding normal tissues. We have reviewed published results for experimental tumors irradiated in situ and either assayed in situ or after excision. The alpha/beta ratios were usually at least as high as those for acutely responding normal tissues, and 36/48 tumors gave values greater than 8 Gy. Low values of less than 5 Gy were obtained for only 4/48 tumors. There are considerable technical problems in interpreting these experiments, but the results do suggest that hyperfractionation might confer therapeutic gain relative to late responding normal tissues on the basis of differences in repair capability. In clinical practice more efficient reoxygenation, cell cycle redistribution and decreased overall treatment time might also confer therapeutic gain.
Increased frequency of certain human leukocyte antigens (HLA) has been reported in various subsets of patients with lupus erythematosus (LE). Specifically, HLA-B8 and HLA-DR3 have been associated with subacute cutaneous LE; HLA-DR3 or HLA-DR2 is found in mothers of infants with neonatal LE; and HLA-A1, HLA-B8, HLA-B15, and HLA-DR2 occur in patients with systemic LE. We typed twenty-two white and nineteen black patients with chronic cutaneous (discoid) LE (DLE) for the A, B, and DR loci of the HLA antigens. HLA-DRw6 was found in an increased proportion of our patients of both races compared with controls. HLA-B8 was found more frequently in white DLE patients than in white control subjects. Thus a genetic predisposition may be a factor that explains the variation in disease expression.
A 22-year-old man presented with a progressive cutaneous eruption consisting of reddish-yellow papules and plaques on his face, which was histopathologically characteristic of a non-X histiocytosis. No systemic involvement was present. Monoclonal antibody staining of the tissue infiltrate was strongly positive for only OKT6. On electron microscopy, Langerhans (Birbeck) granules were not found. Four years of conservative treatment was unsuccessful. Spontaneous involution did not occur. Dermabrasion not only produced excellent cosmetic results, but on rebiopsy the histiocytic infiltrate was absent. There has been no recurrence in treated areas after 18 months.
Serologic and clinical data were obtained from forty patients with discoid lupus erythematosus in 1982. Clinical disease was characterized by quality, extent, severity, activity, photosensitivity, and systemic manifestations. The patient's sera were examined for the presence of antinuclear, anti-Ro and anti-La, anti-ribonucleoprotein and anti-Sm, anti-single-stranded deoxyribonucleic acid (ssDNA), and antinative DNA antibodies. In late 1984, thirty-three patients had follow-up clinical examinations. On the initial evaluation the patients with positive antinuclear antibody (ANA) findings were clinically characterized by a significantly higher incidence of photosensitivity and arthritis, an elevated erythrocyte sedimentation rate, and cutaneous lesions of subacute cutaneous lupus erythematosus. The activity and extent of disease in 1982 did not correlate with the presence of ANA. Elevated levels of ssDNA antibodies were present in seven of the forty patients (significantly greater than control subjects; (p less than 0.005) and correlated with widespread, active discoid lupus erythematosus, an elevated erythrocyte sedimentation rate, and a slightly greater risk of systemic lupus erythematosus in 1982. At the 2-year follow-up examination, thirteen of the seventeen patients with a positive ANA had active clinical cutaneous disease, and ten of the sixteen patients with negative ANA findings had continued activity (not statistically significant). However, all seven patients with elevated ssDNA antibody levels had continued activity, and disease progression had occurred in three. Thus the presence of ssDNA seems to correlate strongly with active, progressive lupus erythematosus. The presence of antibody abnormalities in patients with discoid lupus erythematosus correlates with clinical disease and provides more support for the theory linking discoid lupus erythematosus to systemic lupus erythematosus as part of a continuum.
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