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Biomedical subjects

A Gough

Publications and source records attributed to A Gough.

At least 55 records · Page 3Linked to original sources
PubMed1996

Clinical associations of dual-energy X-ray absorptiometry measurement of hand bone mass in rheumatoid arthritis.

Hand bone mineral density (BMD) measurement by dual-energy X-ray absorptiometry (DXA) has potential as a marker of progression in early rheumatoid arthritis (RA). We examined a DXA methodology and studied in a cross-sectional manner 202 patients with RA. Hand BMD correlated inversely with age and was higher in males. Hand BMD correlated with lumbar and femoral sites. In females, BMD of the hand correlated positively with grip strength and negatively with disability. Those with higher C-reactive protein (CRP) had significantly lower hand BMD than those with normal CRP. In patients with a normal CRP, the hand BMD:lumbar BMD ratios were significantly higher in patients with longer disease duration. Hand BMD correlates with measures of disease activity, functional capacity and also with lumbar and femoral BMD. Hand bone loss occurs in early disease, in the absence of detectable systemic disease, and before lumbar BMD loss. It has the potential to be an outcome measure in early disease.

Absorptiometry, Photon↗
PubMed1996

Malignant intracranial teratoma in a juvenile Wistar rat.

An intracranial malignant teratoma was identified in a 91-day-old male Wistar rat manifesting central nervous system-related clinical signs. This tumor occupied the right midbrain and portions of the right caudal cerebrum and cranioventral cerebellum. Microscopically, the tumor contained intermingled cartilage, bone (with medullary hematopoietic tissue), fibrous connective tissue, skeletal muscle, fat, pseudostratified ciliated epithelium, stratified squamous epithelium, serous and mucoserous glands, and neural tissue with ependymal and choroid plexus epithelia. Poorly differentiated cells with primitive cartilaginous matrix were present throughout the lining of lateral ventricles, in the aqueduct of Sylvius, and in meninges overlying normal cerebellar tissue indicating tumor metastasis occurred via cerebrospinal fluid. This neoplasm was not identified in extracranial sites and hence was considered a primary intracranial malignant teratoma with metastases via cerebrospinal fluid.

Animals↗
PubMed1996

Perspective on the carcinogenic potential of phenytoin based on rodent tumor bioassays and human epidemiological data.

Phenytoin is a hydantoin-type anticonvulsive agent used extensively for nearly sixty years in the prophylactic treatment of grand mal and psychomotor seizures. 2. Based upon somewhat contentious evidence of phenytoin-induced lymphoma in mice and upon epidemiologic evidence of an association between anticonvulsive therapy and lymphoma in epilepsy patients, the International Agency for Research on Cancer (IARC) has collectively regarded these data as limited evidence of carcinogenicity. 3. Two year carcinogenicity studies of standard bioassay design conducted in mice and rats yielded statistically significant increased incidence of hepatocellular adenomas in mice at phenytoin plasma concentrations approximating the therapeutic anticonvulsive range. Tumor incidence in rats was not affected. Previous carcinogenicity studies have found similar increases in hepatic tumor incidence in mice. 4. Phenytoin is a known enzyme inducer and shows tumor promoting activity in chemically initiated mouse liver. Evidence for genotoxicity is weak or equivocal, consequently phenytoin-induced liver tumors appear to occur through nongenotoxic mechanisms. 5. Finally, despite six decades of extensive therapeutic use and thorough epidemiologic evaluation, there is no evidence for an association between liver cancer and phenytoin therapy in epilepsy patients. Thus, hepatocellular neoplasia in phenytoin-treated rodents appears to be of little significance to man.

Animals↗
PubMed1994

Genetic typing of patients with inflammatory arthritis at presentation can be used to predict outcome.

OBJECTIVE: To test the hypothesis that genetic characterization of patients at the time they present with inflammatory arthritis can predict subsequent destructive disease. METHODS: We evaluated 177 patients with early arthritis. Patients were serologically tested for rheumatoid factor (RF) and were DNA oligotyped for the presence of conserved base sequences in the third hypervariable region (HVR3) of the DRB1 gene, previously shown to be associated with severe rheumatoid arthritis (RA). Homozygosity in the patient's genotype was confirmed using restriction fragment length polymorphism analysis. The main outcome measure was radiologic erosions at 1 year. RESULTS: At presentation, 120 patients fulfilled the American College of Rheumatology 1987 criteria for RA, 64% of whom possessed the conserved base sequences, compared with 45% of 347 healthy controls (P < 0.001) and with 56% of 57 patients with other inflammatory arthritis (P not significant). Within the RA population, the frequency of Dw4/Dw14 compound heterozygotes was disproportionately increased. The presence of either HVR3 or RF had a relative risk of 13.49 for erosions, with a sensitivity of 95% (specificity 39%); the presence of both HVR3 and RF had a relative risk of 8.13, with a specificity of 88% (sensitivity 53%). All but 1 patient with the Dw4/Dw14 genotype developed erosions within 1 year. CONCLUSION: Knowledge of a patient's HLA-DR type and RF status allows clinically useful prediction of erosive disease; patients possessing Dw4/Dw14 represent a particularly high-risk subgroup.

Alleles↗
PubMed1994

Induction of small intestinal adenocarcinomas in Wistar rats administered amsacrine.

Amsacrine is an aminoacridine that binds to DNA by intercalation. Because amsacrine interferes with DNA synthesis it has potent genotoxic and cytotoxic properties. To define its tumorigenic nature, amsacrine was studied in a 104-week carcinogenicity bioassay using Wistar rats. Treatment regimen consisted of 6 cycles of intravenous administration over 5 consecutive days followed by 23 days without drug to allow for recovery from cytotoxicity. Doses were 0.25, 1 and 3 mg/kg. At 3 mg/kg mortality was excessive reaching 100% of males by Week 90 and 96% of females at Week 104. Deaths were associated with either tumor induction or cytotoxicity. Multisystemic tumor development manifested in a dose-related fashion. The incidence of small intestinal adenocarcinomas was particularly striking owing to the rarity of these neoplasia in Wistar rats. Small intestinal adenocarcinomas that were well-differentiated presented as pedunculated masses or were sessile masses derived from flat mucosa. Mucin-secreting adenocarcinomas showed poorly-differentiated histologic pattern with absence of crypt or villus structures. We postulate that they are variants of the neoplasia derived from flat mucosa wherein the loss of histologic architecture is the sequela of protracted secretion and accumulation of mucin leading ultimately to extensive tumor remodeling. As amsacrine is primarily excreted in bile, direct exposure to this genotoxic agent was a probable factor in tumorigenesis like small intestinal carcinogens such as 1,2-dimethylhydrazine and azoxymethane.

Adenocarcinoma↗
PubMed1994

Adverse interaction between intramuscular methylprednisolone and sulphasalazine in patients with early rheumatoid arthritis. A pilot study.

A defective hypothalamic-pituitary-adrenal axis has been associated with susceptibility to arthritis in rats and with rheumatoid arthritis in humans. The effect of corticosteroid supplementation in early RA has not been tested previously. We undertook a double-blind placebo-controlled study of sulphasalazine plus either corticosteroid or placebo. No early benefit was demonstrated as 7 of 11 of the corticosteroid supplemented group had withdrawn by 1 year. The addition of corticosteroids to sulphasalazine in patients with early disease did not appear to offer any benefit.

Adult↗
PubMed1994

Sulfate metabolism is abnormal in patients with rheumatoid arthritis. Confirmation by in vivo biochemical findings.

OBJECTIVE: To independently confirm previous probe drug findings that patients with rheumatoid arthritis (RA) have defective oxidation of cysteine derivatives. METHODS: Measurement of cysteine dioxygenase substrate (cysteine) and product (sulfate) under controlled conditions, with elemental assessment by proton induced x-ray emission (PIXE). RESULTS: Plasma inorganic sulfate was significantly depressed in patients with rheumatoid arthritis (RA) compared to both controls and non-RA disease, 85 +/- 36 nm/ml vs 267 +/- 146 and 604 +/- 412 (mean +/- SD. RA patients vs non-RA disease p < 0.001). Fasting cysteine levels were significantly raised compared to controls (59 +/- 20 nm/ml vs 17 +/- 81 nm/ml p < 0.001). Synovial fluid (SF) sulfate was also significantly reduced in patients with RA compared to non-RA controls (202 +/- 117 nm vs 1041 +/- 700 p < 0.001). PIXE data confirmed the low sulfate levels in serum and SF while showing no reduction in the levels of other elements analyzed. CONCLUSIONS: These cysteine/sulfate findings confirm the validity of the previous probe drug abnormalities and the importance of defective cysteine dioxygenase activity in RA.

Adult↗
PubMed1993

Toxicity of CI-949, a novel anti-allergy agent.

The toxicity of CI-949, an effective inhibitor of allergic mediator release in pharmacology models, was evaluated in rodents and dogs. Median lethal doses at 24-hr postdose ranged from 343 to 453 mg/kg in mice and 806 to 2058 mg/kg in rats. Delayed toxicity was observed at 300 mg/kg and greater in mice and at 500 mg/kg and greater in rats. Mortality and clinical intolerance occurred in rats at 200 and 400 mg/kg in the subacute studies, and at 100 and 150 mg/kg in the 13-week study. In rats, dose-dependent lymphoid tissue atrophy and depletion or necrosis of lymphocytes in lymphoid tissues were seen in deaths and moribund terminations. Although doses up to 60 mg/kg administrated for 2 weeks to dogs were well tolerated, 60 and 120 mg/kg in the 13-week dog study were poorly tolerated. Cutaneous sores, mucocutaneous purulent discharge, emesis, diarrhea, and weight loss were identified at these lethal doses. Histopathologic changes in dogs included myocardial, vascular and soft tissue inflammation, and gastric ulceration at 60 and 120 mg/kg, and thymic atrophy at 20 mg/kg and greater. Doses of 10 and 50 mg/kg were no-effect doses in 13-week repeated dose studies in dogs and rats, respectively. These results were used to support initial human clinical trials of CI-949.

Administration, Oral↗
PubMed1992

Increased prevalence of poor sulphoxidation in patients with rheumatoid arthritis: effect of changes in the acute phase response and second line drug treatment.

A minority of normal subjects have an impaired ability to oxidise sulphur, which is associated with an increased risk of side effects when they receive sulphur containing drugs. In 114 patients with rheumatoid arthritis a greatly increased prevalence of poor sulphoxidation was found in 82 (72%) patients compared with 70/200 (35%) healthy controls, 45/121 (37%) controls matched for age, and 4/35 (11%) of the normal aged general population. In a longitudinal study of 37 patients there was no significant alteration in sulphoxidation status after the introduction of a second line drug or with marked changes in the acute phase response. It seems, therefore, that the poor sulphoxidation status in patients with RA is not an epiphenomenon and may be an important factor in determining the clinical features of rheumatoid disease.

Acute-Phase Reaction↗
PubMed1991

Crystallization from concentrated sucrose solutions.

When concentrated aqueous solutions of sucrose are cooled, ice or sucrose crystals separate, depending on the concentration and temperature. The state diagram of the sucrose-water system describes both the equilibrium and non-equilibrium behaviour. A detailed account is given of the effect of sucrose concentration and various, principally polysaccharide, stabilizers on the processes of homogeneous and heterogeneous nucleation, as well as the kinetics of crystal growth. Increasing concentrations of sucrose reduce the diffusion coefficient of water molecules and the linear growth velocity of ice crystals. Polysaccharide stabilizers have relatively little effect until incipient gelation occurs. Thereafter, there is a gross change in crystal form and growth rate. A careful analysis of the impact of sucrose concentration on the rate of ice crystal growth has not permitted satisfactory matching of theoretical predictions with actual behaviour. Recent studies of the rate of growth of sucrose crystals in sucrose glasses of varying water contents are recorded. There is no simple relationship between the moisture content (in the 2-12 w/w % H2O range) and the rate of growth of the sucrose crystals.

Chemical Phenomena↗
PubMed1990

Do normal plasma neurotensin concentrations increase ileal output?

Infusions of neurotensin increase ileal secretion in experimental animals, and the volume of ileal effluent in patients with ileostomies. The aim of the present study was to determine whether normal postprandial plasma concentrations of neurotensin increase the volume of fluid leaving the ileum. Basal and peak postprandial plasma neurotensin concentrations were 23 (17-36) and 39 (25-43) pmol/l (median and range) respectively in five subjects with ileostomies and 15 (3-27) and 32 (15-82) pmol/l respectively in nine normal subjects. Infusion of neurotensin for 30 min at a rate of 6.3 pmol/kg/min into six patients with ileostomies increased ileostomy output about 10-fold, and produced a significant decrease in the concentration of solid material, but plasma neurotensin concentrations rose to 237 (82-422) pmol/l during infusion at this rate. Infusion of neurotensin at 2.3 pmol/kg/min, producing plasma levels of 60 (16-108), had no significant effect the amount or nature of ileostomy effluent. We conclude that normal postprandial plasma concentrations of neurotensin are unlikely to influence the volume of fluid leaving the ileum.

Adult↗