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Biomedical subjects

C M Goodall

Publications and source records attributed to C M Goodall.

At least 19 recordsLinked to original sources
PubMed2001

The association of Cushing's disease and primary empty sella turcica.

The empty sella turcica is defined as the extension of the subarachnoid space toward the intrasellar region with displacement of the pituitary towards the posteroinferior wall. By autopsy studies, the incidence in the general population is around 20%. The association of Cushing's disease (CD) and empty sella has been infrequently reported. In our group, from a total of 68 patients with CD studied by magnetic resonance imaging (MRI), we found the presence of a primary empty sella syndrome (ESS) in 11 (16%). Of these, 9 had partial and 2 total ESS, and in four of them a microadenoma could be identified. Remission, ascertained by subnormal postoperative cortisol levels in blood and/or urine was obtained in 5 of 6 patients operated on by the transphenoidal route. Following surgery, 2 patients presented cerebrospinal fluid (CSF) leakage, 2 diabetes insipidus, and 2 some form of hypopituitarism, figures apparently higher than in non-ESS patients with CD. Ketoconazole was indicated as second line treatment in 2 patients and as primary therapy in 4, resulting in normal urinary free cortisol (UFC) values, with no complications. The relationship of ESS and CD is probably fortuitous given that the frequency of ESS in the general population is similar. Although in empty sella both surgery and radiotherapy seem to have greater risk of complications, surgery remains the first line treatment. Nevertheless, chronic treatment with ketoconazole could be a useful first choice, particularly when no adenoma is seen, or in those who have contraindications for surgery.

Adult↗
PubMed1986

Comparative sensitivity of survival-adjusted chi-square and normal statistics for the mutagenesis fluctuation assay.

Three statistics for analysis of microtitre plate mutagenesis fluctuation tests were studied by simulation, and in enzyme-activated assays of dimethylnitrosamine and diethylnitramine. A survival-adjusted chi 2 statistic ('Gsq') was compared with Katz's normally distributed statistic ('Phi'), and with the survival-independent statistic ('Zsq') of Gilbert. When toxicity was either very low or high, the Phi statistic either could not be evaluated over the whole range of possible background mutant frequencies, or sometimes it indicated unusually high levels of statistical significance, even when the other tests were negative. The survival-adjusted Gsq closely followed the Zsq statistic throughout the experimentally useful range of toxicities and mutant background values, with some improvement in sensitivity. Within the range 80 +/- 10% survival approximately, Katz's statistic 'Phi' was the most sensitive. The choice of statistical test could affect the estimate of the minimal effective mutagenic concentration by a factor of 10-100. For screening unknowns, both types of test (Phi and Gsq (or Zsq] may help in detecting suspect pro-mutagens and in designing a confirmatory assay. Bacterial population statistics are needed to assess the value of statistically positive results.

Cell Survival↗
PubMed1986

Mutagenicity of para-nitroso-dimethyl- and diethyl-anilines.

Low concentrations of para-nitroso-dimethylaniline (NdMA) were mutagenic to Salmonella typhimurium TA100 with optimal effect at 1.5 microM in fluctuation assays, without activating enzymes. The diethyl homologue (NdEA) had little or no mutagenic effect at low concentrations, although the bacteriocidal effects of NdMA and NdEA were similar. At higher bacteriocidal concentrations (approximately LC55-LC80) both NdMA and NdEA were mutagenic. NdMA and some other C-nitroso compounds proved carcinogenic in animal bioassays, and further research is needed to assess the human hazard from exposure to C-nitroso compounds in food, medicines or industry.

Mutagenicity Tests↗
PubMed1985

Correlation of human bladder tumor recurrence with changes in clonogenicity of urothelial cells.

Over a 2-year period 340 cystoscopies were performed on 174 patients (126 men and 48 women) followed up for previously treated transitional cell tumor of the bladder or new cases suspected of having bladder tumor. Bladder washings taken at cystoscopy in 66% yielded cells for clonogenic assay. Patients with transitional cell tumors had an average clonogenic index (CI) of 14 (+/- 5) colonies per 10(5) viable urothelial cells, whereas previously tumorous patients with tumor-free bladders had an average CI of 6 +/- 1 colonies (P less than 0.001, Student's t test). Patients with hematuria but no bladder tumor had an average CI of 8 (not significant). In serial examinations with consecutive successful clonogenic assay, 11 of 16 patients remaining tumor-free had constant or falling CI whereas 9 of 12 patients with recurrent tumor had rising CI values (Fisher; P less than 0.025). Changes in the clonogenic index of cells taken from bladder washings paralleled the changes in tumor status at cystoscopy and might have predictive value in this disease.

Carcinoma, Transitional Cell↗
PubMed1985

Mutagenic activation of dialkylnitrosamines by intact urothelial cells.

Intact urothelial cells isolated from bladders of untreated inbred NZO/BIGd or NZC/BIGd mice and NZR/Gd rats activated dimethyl, diethyl, dipropyl, and dibutyl nitrosamines in a liquid culture mutagenesis fluctuation assay using Salmonella typhimurium TA100 as target organism. Rat and mouse urothelial cells were highly effective at 1.5 X 10(5) cells/ml, in O2 gas phase, and no cofactors were required. Relative mutagenic activities were estimated at equitoxic (LD50) concentrations of the 4 nitrosamines. Nitrosamines with odd-carbon chain substitutents were more active than the C-even compounds. Although dibutylnitrosamine is a powerful bladder carcinogen in both rats and mice while the other 3 compounds very rarely cause bladder tumours, the most active promutagens were dipropyl and dimethyl, followed by diethyl and dibutyl nitrosamines. None were active in absence of urothelial cells. Mouse bladder cells were more active than those from NZR rats. There were sex differences in the mice with NZC males and NZO females predominating, but in NZR rats urothelial cells from male and female animals were equally active. These dialkylnitrosamines are widely distributed in the environment, and our results indicate that direct mutagenic activation in the urothelium could be one factor contributing to the incidence of bladder cancer.

Animals↗
PubMed1984

Enhancement of rat ACT-1 tumor clonogenicity by xenogeneic mouse macrophages.

In vitro growth of rat atriocaval epithelial tumor cells (ACT-1) was enhanced by the inclusion of xenogeneic mouse adherent peritoneal exudate cells (PECs) in a two-layer soft agar system. A linear relationship was found between the number of cells plated and the number of colonies when ACT-1 tumor cells were plated at plating densities of between 1 and 5 X 10(5) cell/60 mm plate (r = 0.9, P less than 0.001). Inclusion of irradiated PECs in the bioassay for tumor stem cells resulted in a two and a half-fold increase in colony formation in three separate experiments (P less than 0.001).

Animals↗
PubMed1984

Carcinogenesis by N-nitrosohexamethyleneimine in NZO inbred mice.

The carcinogenic response of NZO/BlGd inbred mice of both sexes to oral N-nitrosohexamethyleneimine (NHEX) was investigated at 2 differing dose rates, but equal cumulative doses. Mice received 52 mg NHEX (2 mg/g body wt) in drinking water over either an 8-week period (200 mg/l) or a 32-week period (50 mg/l), and were then kept for their natural lifespans. The main sites of tumorigenesis were upper alimentary tract (oropharynx, esophagus, squamous and glandular stomach) and liver. Lymphomas and biliary epithelial tumours were also induced, but lung carcinogenic response was of marginal statistical significance. In contrast to previous reports we found responses in mice very similar to the organ pattern of NHEX carcinogenesis in rats. A comparable previous study in rats found a more marked change in response pattern at the 2 NHEX dose rates but total doses differed by up to 1.6 times in that experiment. With equal total doses of NHEX the mouse tumour patterns at the same 2 dose rates were nearly the same, but there were higher incidences of liver and lung tumours and of lymphomas at the high dose rate, in agreement with the rat study. There were no significant sex differences in carcinogenic response.

Administration, Oral↗
PubMed1984

Unusually high susceptibility of NZR/Gd rats to bladder cancer induction by low doses of nitrosomethylurea.

Inbred female rats of the NZR/Gd strain were exceptionally susceptible to nitrosomethylurea (NMU) toxicity after intravesical instillations. After only 1.0 mg NMU total given in 10 fractions, 100% of NZR rats developed malignant bladder tumours. Transitional cell carcinomas predominated (56%) when the NMU dose interval was 2 weeks, and most tumours were squamous carcinomas (57%) with a 1-week interval.

Animals↗
PubMed1984

Carcinogenicity of nitrosododecamethyleneimine in NZR/Gd inbred rats.

Nitrosododecamethyleneimine (NDMI) was given to NZR/Gd rats by gavage in olive oil solution, confirming its hepatocarcinogenic activity. Twenty male and 20 female rats received 2.5 mg NDMI twice a week for 52 weeks; a further 10 male rats received 25.0 mg twice a week for 12 weeks. Two-thirds of the animals survived more than 2 years. Of the rats given the high dose of NDMI 50% died with hepatocellular carcinomas, as did 8% of the rats receiving the lower dose and 0.5% of untreated rats (p less than 0.001). In NDMI-treated animals the incidence of atriocaval tumours (p less than 0.001) and of lung tumours (p less than 0.025) was also significantly higher than in untreated controls.

Animals↗
PubMed1984

The effects of estrogen on single dose dimethylnitrosamine carcinogenesis in male inbred Crl/CDF rats.

The effect of longterm estrogen treatment (estradiol valerate) on male rats injected i.p. once with dimethylnitrosamine (DMN, 30 mg/kg, with protein starvation), was studied in 167 male inbred Crl/CDF rats. DMN was given at 40 days (immature rats) or at 90 days (mature rats) to investigate the action of carcinogen and hormone at different stages of development. Estrogen reduced life expectancy of male animals, and was associated with greatly increased breast tumour incidence (to 30%) compared with controls (3%, p less than 0.01). DMN alone enhanced lung tumorigenesis (p less than 0.001) and chronic estrogen treatment significantly reduced both the incidence and multiplicity of DMN-induced lung tumours in male rats (p less than 0.001). Also, estrogen treatment lowered the incidence of spontaneous lung tumours (p less than 0.005). The higher incidence of animals with kidney tubular adenomas and carcinomas induced by DMN in both mature and immature rats was statistically significant (p less than 0.001), but estrogen and the age at carcinogen treatment had no effect. Lethal mesenchymal kidney tumours developed in immature rats exposed to DMN (p less than 0.001), but only developed in mature DMN-treated rats if they received estrogen as well.

Adenoma↗
PubMed1984

Dimethylnitramine metabolism in vitro by NZR rat liver slices.

The net metabolism of dimethylnitramine (DMNO) was studied in NZR rat liver slices in tissue culture medium (Dulbecco's MEM). In rats, mice and fish, liver is the principal target organ for DMNO carcinogenesis. Destruction of DMNO in vitro with oxygenated medium was linear with amount of tissue (0.3-3.0 g liver), and with substrate concentration (0.14-4.44 mM). Substrate destruction (initially 0.2 mM DMNO) was linear for 60 min (average rate 0.9 +/- 0.1 microgram DMNO/g liver/min) and then slowed to become linear again at about half the initial rate from 90 min to longer than 5 h. In anoxic (N2) conditions DMNO metabolism slowed or stopped completely after 70 min. Metabolism of dimethylnitrosamine (DMN) was studied in the same preparation. DMN destruction rates were initially about 50% higher than DMNO, but were equal at longer incubation times. Simultaneous metabolism of DMNO and DMN by the same tissue slices showed DMNO rates unaltered in the presence of equimolar DMN (0.24 mM), but DMN rates were 20-40% depressed. No evidence was found for the oxidation of DMN to form DMNO, or for reduction of DMNO to DMN.

Animals↗
PubMed1984

Strain and sex differences in N-nitrosohexamethyleneimine carcinogenesis in NZB, NZC, NZO, and NZY mice.

The carcinogenic activity of N-nitrosohexamethyleneimine [(NHEX) CAS: 932-83-2; hexahydro-1-nitroso-1H-azepine] was studied in male and female mice of the four inbred strains NZB/BlGd, NZC/BlGd, NZO/BlGd, and NZY/BlGd. A total of 158 mice received NHEX treatment; 1,338 untreated controls were used, all kept under identical laboratory conditions for their natural life-spans. Beginning at age 50 days a 1.56-mM NHEX solution (200 mg/liter) was given instead of drinking water for 8 weeks, which resulted in nearly the same total dosage of 0.7 +/- 0.04 g or 5.7 +/- 0.2 mmol NHEX/kg body weight in both sexes of all four strains. In both sexes of all four strains the main types of tumors after NHEX treatment were squamous papillomas and carcinomas of the esophagus, squamous stomach, and oropharynx and hepatocellular carcinomas. Tumors of the hepatic bile ducts, glandular stomach, and lung and malignant lymphomas were also induced by NHEX, but these tumors had a predilection for certain strains only. The incidences of other tumors characteristic of the untreated mice in each particular strain, such as tumors of the ovary in NZC, tumors of the breast in NZY, and tumors of the duodenum in NZO, were not increased significantly by NHEX treatment. The incidence of main tumor types in NHEX-treated mice varied greatly between strains, e.g., esophageal papillomas and carcinomas in 81% of male NZC versus 32% in male NZB mice. Some marked sex differences also emerged in NHEX-treated animals, e.g., the occurrence of liver angiosarcomas only in males of three strains and the 53% incidence of hepatocellular tumors in male NZY mice compared to the absence of liver tumors in female NZY mice.

Animals↗
PubMed1983

Differential toxicity and clearance kinetics of chromium(III) or (VI) in mice.

The acute and subacute toxicities of several chromium(III) and chromium(VI) compounds were determined in NZC and (CxO) mice injected i.p. The distal median lethal doses (more than 10 days after treatment) averaged (17.9 +/- 1.8) X 10(-6) g chromium/g body weight regardless of the oxidation state of the chromium compound injected (chromium(III) sulphate may be an exception), but acute toxicity (3 days) was much greater with chromium(VI) compounds. Acid digests of entire male mice that were administered i.p. one-sixth of the distal LD50, either once or repeatedly at weekly intervals, were analysed to determine the whole body persistence and clearance kinetics of chromium. Mice dosed once with chromium(III) retained 6.5 times more chromium at 21 days than mice treated with chromium(VI). When chromium(III) was given at weekly intervals mice accumulated 6 times more chromium by 8 weeks than chromium(VI)-treated mice, though only the latter showed symptoms of chronic toxicity. Whole body chromium concentrations continued to rise with further chromium(III) treatments, but slowly declined with chromium(VI). Analyses of fecal and urinary excretion confirmed most of the urinary chromium clearance occurred soon after injection, and that chromium excretion from chromium(VI)-treated animals was much faster in both urine and feces than from mice given chromium(III). The differential storage and clearance kinetics of chromium(III) and chromium(VI) compounds may be significant in experimental chromium carcinogenesis studies and in the toxicology of chromium in workers exposed industrially to potentially carcinogenic chromium-containing dusts or aerosols.

Animals↗
PubMed1983

Enhancement by testosterone of dimethylnitrosamine carcinogenesis in lung, liver and kidney of inbred NZR/Gd female rats.

The effect of androgenic treatments on single dose dimethylnitrosamine (DMN) carcinogenesis was studied in 60 female NZR/Gd inbred rats, 25 of which were intact and received DMN 20 mg/kg i.p. in one dose after 48 h starvation, while 35 received DMN combined with testosterone injections every 4 weeks beginning 15 days before or after DMN, and in 29 rats combined also with ovariectomy. Sixteen female rats underwent ovariectomy and received testosterone every 4 weeks with no DMN. There were also 107 untreated intact contemporaneous control female rats. A single dose of DMN induced alveologenic lung (16%), hepatocellular (24%) and kidney epithelial (44%) tumours in intact rats, and the incidences of lethal tumours at these sites were significantly enhanced by androgenic treatments following the carcinogen, most markedly in the kidney. Androgenic treatment given before DMN injection had no significant effect on kidney or liver tumour incidences, but the carcinogenic response in lung was still strongly enhanced.

Animals↗
PubMed1981

Age-specific incidence of neoplasms in untreated NZR/Gd rats: an inbred strain with cardiovascular tumours and liver glycogen storage disease.

NZR/Gd is a new inbred strain of albino rats subject to epithelial mesotheliomas of the heart and also to hepatic glycogen storage disease. The age-specific incidences of neoplasms in 650 untreated NZR rats are tabulated by sex and histopathologic type. In males the most common neoplasms were artio-caval mesotheliomas (12 per cent.) and lung adenomas (10 per cent.), while in females most were pituitary adenomas (23 per cent.), lung adenomas (10 per cent.) or tumours of breast (7 per cent.), heart (4 per cent.) or liver or uterine cervix (3 per cent.). Uncommon tumours (less than 2 per cent.) were pancreas islet cell adenomas, lymphoma, hemangioma, fibroma or tumours of kidney, ovary or bile ducts. The detailed histopathology of the artio-caval tumours reported earlier was confirmed, but it now appears there is a male preponderance (4 : 1), and larger tumours showed their malignancy by invasion of adjacent structures and occasionally by distant metastasis. In males the primary site was evenly divided between right atrium and inferior vena cava. Metastasis of tumours of all types was uncommon, but multiple primary tumours were frequently found, especially in the endocrine system of female rats. Almost one-third of the tumours were associated with at least one other neoplasm arising in a different tissue. Overall tumour statistics in NZR/Gd rats were quite similar to other inbred strains for which quantitative reports are available, and the virtual absence of other diseases and long life-span (up to 1250 days) indicated no serious effect of the hepatic glycogen storage disease on survival. The NZR rats seem to be unique in producing atrio-caval mesotheliomas, and they have a much higher incidence of alveolar lung adenomas (10 per cent.) tham other reported strains.

Age Factors↗
PubMed1980

Fluoridation and cancer mortality in New Zealand.

Claims that fluoridation of the municipal water supply causes cancer in humans have not been substantiated by independent objective studies in the United States of America, Canada, or New Zealand. After thorough reexamination of the earlier publications from other countries, and our own study of data available for the New Zealand population, we consider the 1976 statement of the Royal College of Physicians seems more than ever justified: "There is no evidence that fluoride increases the incidence or mortality of cancer in any organ".

Aged↗
PubMed1977

Partial inhibition of primary lung tumourigenesis by tetramisole.

Continuous treatment of mice with tetramisole (TMS, approximately 8 mg/kg/day) resulted in a highly significant (p < 0.002) reduction in numbers of primary lung tumours forming in response to neonatal urethane injection. Kinetic study indicated the slopes of the oncogenesis response curves differed, but not significantly. Therefore inhibition of primary lung tumourigenesis was only partial, even though TMS was given during the early stages of tumour development, continuously, and at near maximum tolerable dosage.

Animals↗