Biomedical subjects
Publications and source records attributed to M Robinson.
OBJECTIVE: To test the endoscopy audit protocol for larger prospective study. METHOD: Prospective medical audit. RESULTS: Sixty two endoscopies provided both patient data and suggestions for improvement in the protocol.
This study describes for the first time the complete molecular species composition and turnover of [3H]arachidonic acid in various glycerophospholipid classes of rat erythrocytes, a model system that has been extensively used to investigate numerous membrane phenomena. Quantitative analysis of the individual molecular species of the choline, ethanolamine, serine, and inositol glycerophospholipid classes was possible by preparing their diradylglycerobenzoate derivatives that can be quantitated by on-line uv detection in conjunction with high-performance liquid chromatography; turnover of the molecular species containing arachidonate was evaluated in erythrocytes labeled with [3H]arachidonic acid. A unique observation was the significant amounts of 22:6-20:4, 20:4-20:4, and 18:2-20:4 species observed in the diacyl fractions of phosphatidylethanolamine and phosphatidylserine. Moreover, the analysis of the specific radioactivities of individual phospholipid species from erythrocytes incubated with [3H]arachidonic acid demonstrated a selective incorporation of arachidonic acid into the most highly unsaturated molecular species in all of the phospholipid classes examined. Although the 22:6-20:4, 20:4-20:4, and 18:2-20:4 species represented only 4.5% of the total mass of the diacyl phosphoglycerides, these species accounted for a major portion (37%) of the arachidonic acid incorporated into the phospholipids. These results demonstrate the existence of unique populations of phospholipid molecules in rat erythrocytes with a high degree of unsaturation that exhibit a very rapid metabolic turnover rate.
Since March 1980, 309 patients with anaplastic small cell carcinoma of the bronchus (ASCB) have received remission induction therapy prior to randomisation to maintenance (M) or no maintenance (NM) chemotherapy. Induction therapy consisted of six courses of vincristine, doxorubicin and cyclophosphamide (VAC) given IV every 3 weeks. Those with limited disease also received mediastinal irradiation. Consenting patients with no unequivocal residual disease were randomised to have no further treatment until relapse or a further eight courses of VAC, at a lower dosage, every 4 weeks. Patients failing to achieve randomisation status received palliative treatment only. The median survival for all patients with limited disease (LD) is 363 days and that for patients with extensive disease (ED) is 272 days (P less than 0.00001). Sixty-one patients with ED were randomised. Those having maintenance chemotherapy lived significantly longer (median 372 days) than those who did not continue therapy (median 259 days) (P = 0.006). An imbalance in the proportion of 'complete remitters' randomised to maintenance therapy does not account for this difference. There is no significant difference between the M and NM groups in the 32 randomised LD patients. Continuing treatment during remission with agents used to induce the remission can prolong survival in patients with extensive stage ASCB.
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This investigation was conducted to evaluate the effect of gavage vehicles on altering the severity of the subchronic hepatotoxicity of carbon tetrachloride (CCl4). Male and female CD-1 mice were gavaged with 0, 1.2, 12, and 120 mg/kg CCl4 in either a corn oil or 1% Tween-60 vehicle once daily for 5 consecutive days per week for 90 days. The study revealed that the hepatotoxicity was greater in the mid- and high-dose groups of mice that had received CCl4 administered in corn oil. Increases in serum enzyme activities were detected in the mid-dose groups of mice that were gavaged with CCl4 in corn oil. The serum enzyme activities were significantly higher in the high-dose groups of animals in which CCl4 was administered in corn oil. Histopathological findings indicated that hepatocellular changes following the administration of CCl4 at the mid- and high-dose levels were more frequent and more severe when CCl4 was given in corn oil than when it was administered in Tween-60. The experimental findings indicate that the no-observed-adverse-effect level from CCl4 exposure was lowered by an order of magnitude (from 12 to 1.2 mg/kg) and that the hepatotoxicity of CCl4 was enhanced in the high-dose treatment groups when corn oil was employed as the gavage vehicle.
Stool samples from 83 Sudanese children with gastro-enteritis were examined using a safranin-methylene blue stain. Five children (6.1%) were excreting cryptosporidium oocysts but no other potential enteropathogens. The clinical features of anorexia, vomiting and pyrexia and the profuse green watery offensive stool were similar to those reported previously. All of the children were dehydrated. None of 37 children studied who did not have gastro-enteritis was excreting oocysts.
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Fifty children with drug resistant epilepsy were treated with the Medium Chain Triglyceride (MCT) Emulsion diet. Eight achieved complete control of seizures (four without anticonvulsant drugs), and with the addition of anticonvulsants four had seizures reduced in frequency by 90% and 10 by 50-90%. The best results were obtained with astatic myoclonic and absence seizures, but control of seizures was improved in four children with tonic-clonic and three with complex partial seizures. Food given at the same time as MCT helped to reduce side effects, and an extra dose of MCT before bedtime improved control of nocturnal seizures.
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Lesions that were considered naturally occurring were surveyed in female SENCAR mice used in short-term bioassays. These lesions were encountered in selected target organs and in organs and tissues with gross lesions encountered at necropsy. The genitourinary system was the most frequent site for lesions; cystic ovaries, cystic endometrial hyperplasia, and glomerulonephritis were commonly encountered in this system.
The responsiveness of SENCAR mouse skin to 20 different chemicals with known carcinogenic properties was assessed in initiation/promotion experiments. The purpose of these experiments was to evaluate the extent of false negative responses in mouse skin initiation/promotion protocols and to determine the extent to which early papilloma development can be used to predict the eventual development of malignant tumors. The chemicals were administered as initiators by four different routes: oral, intraperitoneal, subcutaneous, and topical. Following the initiating dose of carcinogen, the animals were subjected to topical applications of 1 microgram 12-O-tetradecanoylphorbol-13-acetate (TPA) 3 times per week for a period of 20 weeks. The yield of papillomas at 24 weeks was selected as a potential predictor of carcinoma yields at 52 weeks following the start of the promotion schedule. Positive responses were observed with only eight of the compounds tested. Where positive results were observed, there was some evidence that the response could depend both qualitatively and quantitatively on the route of administration. However, no route was clearly superior, i.e., different chemicals gave greater responses by different routes. Papilloma yield at 24 weeks following the start of the promotion schedule was clearly related to the development of carcinomas at 52 weeks. No simple linear relationship existed between papilloma yield and carcinoma development, since the number of malignant tumors per papilloma decreased with increasing papilloma yields. The relationship between papilloma and carcinoma yields appeared to be independent of the carcinogen used. These data indicate that there are some limitations in using mouse skin initiation/promotion experiments as the sole basis for identifying substances with carcinogenic activity.(ABSTRACT TRUNCATED AT 250 WORDS)
The term myeloid hyperplasia has been used interchangeably with many other terms to describe an increased production of granulocytes, megakaryocytes, and erythrocytes in the spleen and other organs in the mouse. This process is occasionally misdiagnosed as granulocytic leukemia. This paper reviews some of the terms used interchangeably with myeloid hyperplasia and describes criteria that can be used to differentiate myeloid hyperplasia from granulocytic leukemia. Additionally, the results of a study in which myeloid hyperplasia was induced following the formation of skin tumors in SENCAR mice is discussed. In this study, positive correlations were found between skin lesions, the spleen weight, and histologic appearance of the spleen. The liver rarely showed microscopic changes of myeloid hyperplasia unless the spleen weighed at least 1.0% of the body weight.
To test the feasibility of employing a combined lung adenoma/skin papilloma assay for broader detection of chemical carcinogenesis than that realized with either bioassay done separately, four strains of mice, SENCAR, BALB/c, A/J, and ICR-Swiss, were administered carcinogens either by the oral or intraperitoneal (IP) routes. The carcinogens administered were ethyl carbamate (EC), benzo(a)pyrene [B(a)P], N-[4-(5-nitro-2-furyl)thiazolyl]formamide (FANFT), and acrylamide (ACR). Starting 2 weeks later, 1 to 5 micrograms (depending on strain) of 12-O-tetradecanoylphorbol-13-acetate (TPA) in 0.2 mL acetone/mouse was applied three times weekly to the shaved back for 20 weeks. All strains displayed increases in the yield of lung adenomas in response to EC at 32 weeks. B(a)P increased lung adenomas in only the SENCAR and A/J strain. Only the SENCAR and ICR-Swiss mice gave positive responses in the skin. In the SENCAR mice, positive response was seen with all four chemicals, however, FANFT gave an inconsistent response. The ICR-Swiss mice responded with an increased skin papilloma yield only to EC. In a separate experiment involving only SENCAR mice, animals were treated with a single oral dose of diethylnitrosamine (DEN) followed by triweekly application of 1.0 microgram TPA. This treatment resulted in 51/57 animals developing lung adenomas vs. 5/57 in the control animals. No treatment-related skin tumors resulted with DEN. Histopathologically confirmed lesions indicate that the spectrum of chemicals detected in the SENCAR mouse may be broadened using a combined bioassay that examines both lung and skin responses.
The skin and lung tissues from SENCAR mice used as part of the Environmental Protection Agency's (EPA's) Carcinogenesis Testing Matrix were examined. This study included SENCAR mice used in three different short-term bioassay protocols in which the skin papilloma assay was used to identify initiators, promoters, and complete carcinogens. Also included were the pathology findings from SENCAR mice used in the combined bioassay in which the skin assay and the lung adenoma assay were conducted simultaneously. The gross and microscopic features of treatment-associated and spontaneous lesions of the skin and lung of the SENCAR mouse used in these studies are defined and the lesions most commonly observed are described. Generally, gross observations and microscopic findings in both the skin and lung tissues were poorly correlated. Although there are several definite criteria on which gross interpretations of the various skin and lung lesions can be made, with the exception of pedunculated squamous cell papillomas and the classic squamous cell carcinomas, the various lesion types had a wide variety of clinical presentations that severely compromised the accuracy of gross diagnosis. Further, in the case of benign skin neoplasms, malignant transformation of these tumors most often occurred at the base of the lesion and was initially hidden from gross observation. As a result, approximately 50% of the neoplasms interpreted clinically as benign tumors (papillomas and keratoacanthomas) were actually malignant neoplasms. Moreover, many lesions determined grossly to be nontumorous were in fact found to be neoplastic when examined microscopically. The SENCAR mouse was found to be more responsive in the lung adenoma assay than other strains examined with exception of the Strain A. Although accurate interpretation of the lung lesions in the SENCAR was compromised by nonneoplastic treatment-associated and/or spontaneous lesions, the feasibility of using the SENCAR skin and lung as target tissues in two-stage combined carcinogenesis studies merits further consideration.
Five toxicological tests were performed using concentrated drinking water samples collected at a pilot-scale drinking water treatment plant that had streams treated with different disinfectants (no disinfectant, ozone, chlorine dioxide, monochloramine, or chlorine) before treatment with granular activated carbon (GAC). The toxicological tests used in this study were the Ames Salmonella assay, a subchronic in vivo toxicity assay in mice, the SENCAR mouse skin initiation-promotion assay, a rat liver foci assay, and the lung adenoma assay in strain A mice. These tests were conducted to determine the general toxicity and the mutagenic/carcinogenic potential associated with the use of disinfection and/or GAC in the treatment of drinking water. The stability of the mutagenic activity of the samples tested was determined by repeated analysis using the Ames Salmonella assay. Results indicated that the samples remained mutagenic for the duration of the tests. All the drinking water concentrates (4000 X) prepared by the XAD resin adsorption procedure failed to provide statistically significant indication of carcinogenic activity in the SENCAR mouse, rat liver foci, and the lung adenoma assays. However, concentrates of the chlorine, chlorine dioxide, and monochloramine treated waters gave consistent mutagenic responses in the Ames Salmonella assay. GAC was effective for 6 months in removing both the mutagenicity of chlorine-treated water and the potential of water to become mutagenic when treated with chlorine. In the in vivo, subchronic 30-day toxicity test in mice, some statistically significant differences in organ weights and body weights of animals exposed to different concentrates of some of the samples were observed. However, a consistent pattern of these differences indicating overt toxicity was not detected.
Female SENCAR mice were treated with aqueous solutions of hypochlorous acid (HOCl), sodium hypochlorite (NaOCl), chlorine dioxide (ClO2), and monochloramine (NH2Cl) by whole body exposure (except head) for a 10-min period for 4 days in the first experiment and for 1 day (except NH2Cl) in the second experiment. Animals were sacrificed the day following the last treatment (experiment 1) or on day 1, 2, 3, 4, 5, 8, 10, and 12 following treatment (experiment 2), and skin thickness was measured by light microscopy at X400 by use of an eyepiece micrometer. Concentrations of disinfectants were 1, 10, 100, 300, and 1000 mg/L, for experiment 1 and 1000 mg/L for experiment 2. Thickness of the interfollicular epidermis (IFE) for control animals was 15.4 +/- 1.5 micron. After 4 days of treatment at 1000 mg/L, HOCl and ClO2 increased thickness to 39 +/- 7.0 and 40.2 +/- 11.8, and NaOCl increased thickness to 25.2 +/- 6.1 micron. Only HOCl and ClO2 were tested at 300 mg/L, yielding an IFE thickness of 30.0 +/- 13.1 and 16.8 +/- 0.8 micron, respectively. The response to HOCl was found to be dose-related; the minimally effective dose was 100 mg/L. In earlier, preliminary tests to determine optimum treatment schedule, the response to HOCl appeared to be maximal after 4 days of treatment and tended to decrease with further treatment. The time-course study following a single treatment of 1000 mg/L HOCl, however, showed a progression of IFE thickening of from 18.3 +/- 1.4 at 1 day to 30.8 +/- 8.0 at 8 days, decreasing to 19.1 +/- 6.2 micron at 12 days.(ABSTRACT TRUNCATED AT 250 WORDS)