The relationship between organized medicine and Blue Shield.
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History of Medicine↗
Biomedical subjects
A J Ingram
Publications and source records attributed to A J Ingram.
Health manpower to meet rural-urban needs.
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Health Workforce↗
DNA adducts produced by oils, oil fractions and polycyclic aromatic hydrocarbons in relation to repair processes and skin carcinogenesis.
Ten polycyclic aromatic hydrocarbons (PAHs) mainly with three or four aromatic rings were tested for their ability to induce DNA adduct formation in mouse skin. Four of these were selected to investigate adduct formation and loss over a period of 8 days. Three mineral oils were also examined for their adduct forming ability and one was selected for adduct formation and loss over a period of 8 days. In addition, fractions derived from the same oil containing 2-3- and 4-6-ring aromatic compounds were applied to mouse skin in a non-carcinogenic oil vehicle and adduct levels were observed over an 8-day period. It was found that PAHs that had no mutagenic, initiating or carcinogenic activity and those that had mutagenic activity in bacteria but no initiating activity in mouse skin failed to produce DNA adducts in mouse skin. Two of the three PAHs with initiating activity and both complete carcinogens produced clear evidence of adduct formation, the adduct levels produced by complete carcinogens being 100-1000 times greater than those produced by initiators. Examination of adduct formation and loss with the carcinogenic PAHs benzo[a]pyrene and 5-methylchrysene over an 8-day period showed a peak at 24 h and an apparent two-phase process of adduct loss. It is suggested that the first steep loss was due to DNA repair and that the more gradual subsequent loss was probably due to epidermal hyperplasia and desquamation. With the initiator 1, 4-dimethylphenanthrene (three rings) a peak of adduct formation was seen at 2 days and adduct levels were not reduced much by 8 days. This suggested that, with initiators, adduct formation and repair may be spread over a longer period than with complete carcinogens. With the whole oils, clear evidence of adduct formation was seen with both a carcinogenic non-solvent-refined oil and with a non-carcinogenic residual oil. The level of adduct formation with the residual oil, however, was much lower than with the carcinogenic oil. When adduct formation by the carcinogenic oil was examined over 8 days, the pattern of adduct formation and loss was similar to that of a tumour initiator rather than a complete carcinogen. Peak adduct levels on the diagonal of the thin-layer chromatography (TLC) plates seemed to occur at 1 and 4 days after treatment, with no clear reduction after 8 days. From examination of adducts formed by the 2-3-ring and 4-6-ring aromatic fractions, it appeared that the main adduct spots produced by the carcinogenic oil were due to the 2-3-ring aromatic components of the oil. Adduct spots near the vertical axis of the TLC plates were also seen with the 2-3-ring and 4-6-ring fractions. The relevance of these spots is uncertain, but if they truly represent adducts, the findings suggest that they are due mainly to 4-ring PAHs. The studies suggest that the activity of carcinogenic oils is largely due to substituted 3- and 4-ring polycyclic aromatic compounds and that more attention should be paid to substituted 3-ring compounds in predicting the carcinogenic potential of oils from analytical data.
Animals↗
The dermal bioavailability of radiolabelled benzo[a]pyrene from acetone or from oils of differing viscosity, assessed by DNA and protein binding.
Tritium-labelled benzo[a]pyrene ([3H]BaP) was applied to mouse skin in acetone or mineral oils of differing viscosity. Epidermal DNA and protein were extracted after 24 or 48 h and the degree of adduct formation determined by the radioactivity present. When [3H]BaP was applied in acetone, the degree of DNA and protein binding was around 15-20 times greater than that observed when a low-viscosity oil was used as a vehicle. When applied in oils of differing viscosity, however, only a twofold difference was seen across the whole viscosity range (13.5 cSt* at 40 degrees C to 1665 cSt at 60 degrees C). From measurements made of urine and faecal radioactivity and from small-scale investigations using other routes of administration, it was clear that the grooming activity of the animals had a marked effect on skin absorption and macromolecular binding. It is possible that greater grooming activity with low-viscosity oils may explain why oil viscosity did not have a greater effect on binding levels, but further studies are needed to investigate this. These findings may have important implications in the interpretation of long-term skin painting studies and may assist in the interpretation of analytical data and short-term biological assays.
Acetone↗
The early changes in mouse skin following topical application of a range of middle distillate oil products.
A white spirit/naphtha, three kerosines, two gas oils and a catalytically cracked light cycle oil (LCO) were applied topically to mice, three times a week for up to 6 weeks, and skin changes were examined histopathologically at intervals. The changes within 1 week of treatment appeared to depend on the effect that the physicochemical properties of each type of product had on their penetration through the skin surface or via hair follicles. With white spirit the most prominent change was widespread epidermal necrosis occurring after the second treatment, implying that the lowest boiling point materials penetrate mainly through the surface epidermis. The earliest effects with kerosines were within and around hair follicles with epidermal degeneration developing later, suggesting a predominance of follicular entry. Gas oils and LCO produced similar changes to kerosines within 1 week, gas oils producing a slower and less severe response and LCO a more severe response. In skin examined after 1-6 weeks of treatment with all middle distillates, repeated cycles of necrosis and healing responses were evident; this implied that once the epidermal barrier layer had been damaged, follicular entry became less important. The severity of the skin changes observed with these middle distillates was probably sufficient for skin tumours to arise by a non-genotoxic mechanism if a similar treatment regime was used in a long-term skin painting study. A method of avoiding excessive skin irritation is therefore essential in such a study in order to obtain a reliable prediction of the human hazard of such materials.
Administration, Topical↗
An investigation of the main mutagenic components of a carcinogenic oil by fractionation and testing in the modified Ames assay.
A low-viscosity carcinogenic oil was extracted with dimethylsulphoxide (DMSO) and the extract fractionated into 1-3 ring aromatic components, 4-6 ring polycyclic aromatic compounds (PCAs) and polar materials. Each of these fractions was tested in the Mobil modified Ames assay at the same concentration as in the DMSO extract, alongside unfractionated DMSO extracts from the same oil and two reference oils. In addition the fractions were combined in various ways to examine inhibitory or additive effects. Clear positive findings were obtained with the DMSO extract of the main test oil, with some reduction in activity in a sample (the starting material for fractionation) that was back-extracted to remove DMSO. Of the three fractions tested on their own and assessed in terms of mutagenicity index, the 1-3 ring aromatic fraction had the greatest mutagenic activity, showing similar activity to the starting material, whereas the 4-6 ring PCA fraction had much lower activity and the polar fraction showed the lowest activity with an absence of doubling in one of the tests. The polar fraction showed signs of an inhibitory effect on the response to the 1-3 ring aromatic fraction and to a questionable extent on that of the 4-6 ring PCA fraction. Although a low level of the 4-6 ring PCA fraction showed some inhibitory effect on the response to the 1-3 ring aromatic fraction, a low level of the 1-3 ring aromatic fraction added to the 4-6 ring PCA fraction enhanced the response.(ABSTRACT TRUNCATED AT 250 WORDS)
Carcinogens↗
Factors affecting the bioavailability of benzo[a]pyrene from oils in mouse skin: oil viscosity, grooming, activity and its prevention.
In the main study, tritium-labelled benzo[a]pyrene ([3H]BaP) was added to oils of a wide range of viscosity (from 13.5 to ca. 8000 cSt at 40 degrees C) and these were applied once to mouse skin under conditions where grooming was either allowed or prevented. The binding of [3H]BaP to epidermal protein and DNA was assessed. In addition, some studies were conducted to investigate the effect of prior oil exposure on binding levels and to compare binding levels following single and multiple application. It was found in the main study that the binding of [3H]BaP to both DNA and protein was increased as the viscosity of the oil vehicle decreased. Whereas only a twofold difference in DNA binding was found between the lowest and highest viscosity oil vehicle if grooming was allowed, a 14-fold difference was seen if grooming was prevented. This was due to much higher binding levels with low viscosity oils when grooming was prevented. Protein binding showed similar results, although the difference between the grooming and non-grooming situations was slightly less. Whether grooming was prevented or not, both DNA and protein binding of [3H]BaP were found to be inversely proportional to the logarithm of viscosity of the oil vehicle, but when grooming was prevented, the slope for DNA binding was 10 times steeper than when it was permitted. Exposure of the skin to either high or low viscosity oils prior to the application of [3H]BaP in the same oil inhibited the binding to DNA but not to protein.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
DNA adduct formation by mineral oils and their fractions as indicated by 32P-postlabelling: is adduct formation truly indicative of carcinogenic potential?
Oils of differing types, physical properties and carcinogenic activity were tested for ability to produce epidermal DNA adducts 24 h after application to the skin of mice, using the 32P-postlabelling method. Two studies were carried out, the first on three oils to identify the adduct-forming components, and the second on nine oils to investigate whether the nature of the oils affected their adduct-forming potential. In addition to the whole oils, fractions of the oils containing saturated hydrocarbons, 2-6-ring aromatic compounds and polar compounds were tested in both studies in proportion to their concentration in the original oil. In addition, a further examination of the aromatic fractions from two carcinogenic oils was carried out in the first study by testing 2-3-ring and 4-6-ring subfractions (the latter containing carcinogenic polycyclic aromatic compounds (PACs)). Results from the first study indicated that carcinogenic oils do produce adducts and that the adduct-forming components were mainly in the aromatic fraction. When, however, subfractions of the aromatic fraction were examined, it was found that slightly higher adduct levels were produced by the 2-3-ring aromatic fraction than with the 4-6-ring PAC fraction. This was contrary to expectation from published work on the skin carcinogenicity of oils and suggested that some non-carcinogenic PACs may produce adducts. The second study indicated that although most carcinogenic oils produced adducts, some non-carcinogenic oils can also do so.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Early changes produced in mouse skin by the application of three middle distillates.
It has been reported by the American Petroleum Institute (API) that dermal applications of certain middle distillates of mineral oils can result in high incidences of skin tumours in mice. This was unexpected as the polycyclic aromatic hydrocarbon (PAH) levels in these were below detection limits. To examine the possible role of tissue injury in the induction of tumours, the skin reactions produced by thrice weekly applications of three middle distillates similar to those tested by the API were examined grossly and histopathologically at intervals up to 6 weeks. Various reference materials and oils were used as controls. Preliminary histological examination showed that severe skin damage was present from week 1 onwards in mice treated with the three middle distillates, two of them producing epidermal loss and ulceration. Marked epidermal hyperplasia was produced by all three middle distillates. These findings support the view that regenerative epidermal hyperplasia due to repeated severe skin damage may have exerted a powerful promotional effect in the production of the skin tumours by middle distillates in the API study.
Animals↗
The clinical utility of Doppler ultrasound prior to arteriovenous fistula creation.
Arteriovenous fistula (AVF) is the preferred access for long-term hemodialysis, with superior long-term patency rates; however, early failure rates are significant. Recent evidence has brought into question the preferred site of AVF creation in many patient groups. A preoperative test that could reliably predict the outcome of a proposed AVF would be of great benefit. Doppler ultrasound has been the most extensively studied and widely used test to guide access creation. Accurate and validated measurements of internal vessel diameter, both arterial and venous, and blood flow in the upper extremity are obtainable by Doppler ultrasound. Studies evaluating the utility of Doppler ultrasound prior to AVF creation suggest that vessel size and blood flow are predictive of AVF outcome. An AVF created using a cephalic vein and/or radial artery smaller than 1.5-2.0 mm is likely to fail; such preoperative data may indicate that an upper arm AVF should be the primary access attempted. Further prospective studies are needed to evaluate the utility of Doppler ultrasound.
Arteriovenous Shunt, Surgical↗
Nonunion treatment with pulsed electromagnetic fields.
Noninvasive, pulsed electromagnetic field treatment, when properly employed, was effective in securing healing of ununited fractures in 64.4% of 149 patients. The effectiveness of this modality can be ascertained after three months of intensive use in more than 85% of patients, thus enabling the clinician to decide to terminate treatment, continue electrostimulation, or abandon it in favor of another treatment modality. The success of treatment is dependent upon certain variables. Anatomic location of the nonunion is important. Higher healing rates were noted in the tibia than in the femur or humerus. In some conditions, combined electrostimulation and bone grafting was more effective than either measure alone. Young patients healed more rapidly than older patients. Electrostimulation is more effective when instituted within two years of the original fracture than when started at longer intervals after the injury. Infection, either quiescent or actively draining, does not seem to affect the overall results. Of greatest importance is patient adherence to the treatment protocol as outlined, with emphasis placed on adequate immobilization of the fracture and absolute nonweight-bearing during treatment. Considering these factors and in light of the very rare frequency of short-term side effects, the use of pulsed electromagnetic fields appears to be a reasonable choice of treatment in the management of ununited fractures.
Adolescent↗