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Biomedical subjects

G Doyle

Publications and source records attributed to G Doyle.

27 records · Page 2Linked to original sources

DNA repair synthesis in individuals with and without a family history of cancer.

The influence of family history on DNA repair synthesis, unscheduled DNA synthesis (UDS), was assessed in volunteers with or without a family history of cancer. UDS, following treatment of mononuclear leukocytes with N-acetoxy-2-acetylaminofluorene, was measured as the incorporation of [3H]thymidine into DNA in the presence of hydroxyurea. The positive family history group (n = 71) had an average of 2.4 first-degree relatives with cancer, defined as any major cancer, excluding skin cancer: 31 participants reported that cancer occurred in both their parents. The "no family history' comparison group (n = 29) had no family history of cancer through the second degree. There was a significant reduction in UDS in cells from individuals with family history, compared to those with no family history (P greater than 0.002). This relationship was not explained by factors known to influence UDS, such as age, smoking or hypertension. We conclude that reduced UDS in mononuclear leukocytes is associated with a family history of any major cancer, and is not confined to a history of cancer of any single organ site. This conclusion is further supported by the observation that individuals (n = 13) with parents who had an earlier onset of cancer (less than 60 years) also had a significantly lower DNA repair synthesis than those (n = 18) whose parents had later diagnosis of cancer (greater than 60 years).

Acetoxyacetylaminofluorene↗

Demonstration of shared antigenic determinants between Streptococcus mutans BHT cell membrane, human heart tissue and myosin using monoclonal antibodies to S. mutans.

Monoclonal antibodies (MAb) raised to intact Streptococcus mutans P-4 cells (serotype e) were used to demonstrate the presence of shared antigenic determinant(s) between S. mutans BHT (serotype b) cell membranes and human heart tissue. MAb binding to both BHT membrane and human heart tissue was demonstrated by ELISA. Common antigens were identified by immunoblot analysis following separation of BHT membrane components and human heart antigens by SDS-PAGE. MAb 22C4 recognized three polypeptides from the BHT membrane preparation, having molecular masses of 42, 56 and 85 kDa. MAb 22C4 also recognized an 85 kDa component and a 200 kDa component from human heart tissue. MAb D159 was specific for a single 82 kDa polypeptide in BHT membrane, and also bound to two high molecular mass components in human heart (165 and 200 kDa). When both MAb D159 and 22C4 were first absorbed with S. mutans P-4 cells, subsequent reactivity to the aforementioned BHT membrane components was inhibited, indicating that these cross-reactive components are found in S. mutans P-4 as well as in S. mutans BHT micro-organisms. Competitive binding analysis showed that both MAb D159 and MAb 22C4 bound to myosin, indicating that S. mutans BHT membrane, human heart tissue and myosin share at least one immunodeterminant. This indicates that myosin could be the cross-reactive tissue component in human heart.

Antibodies, Bacterial↗

Pharmacokinetics of enalapril in normal subjects and patients with renal impairment.

The pharmacokinetics of enalaprilat were studied after administration of single and multiple doses of enalapril maleate to people with normal and impaired renal function. Renal impairment was associated with higher serum concentrations of enalaprilat, longer times to peak concentrations, slower decline of serum concentrations and with reduced urinary elimination. Urinary elimination of enalaprilat was closely related to renal function. In patients with severe renal impairment (GFR values below 30 ml min-1 1.73 m-2) significantly smaller doses of enalapril maleate will be required than in patients with normal or less severely impaired renal function.

Adult↗

Dental caries vaccine: some problems solved?

The interest in a dental caries vaccine has been great over the past few years. Studies have shown two possible problems using Streptococcus mutans as an immunogen: (i) the production of heart reactive antibody, and (ii) the need to protect against several serotypes. Possible solutions to these problems are discussed.

Animals↗

Carcinoma of the oesophagus associated with membrano-proliferative glomerulonephritis.

Nephrotic syndrome has been observed in association with different types of neoplasia. This appears to be the first report of the occurrence of the nephrotic syndrome due to membrano proliferative glomerulonephritis in association with carcinoma of the oesophagus. Although proteinuria was present before excision of the tumour, the nephrotic phase occurred subsequently. Eventually it disappeared leaving the patient with a clear urine and biochemical and histological improvement of the renal lesion (including immunofluorescent and electronmicroscopy studies). Possible mechanisms responsible for the nephrotic syndrome in this case are discussed.

Carcinoma, Squamous Cell↗

Solubilized ibuprofen: evaluation of onset, relief, and safety of a novel formulation in the treatment of episodic tension-type headache.

OBJECTIVE: To evaluate the relative efficacy of a new solubilized formulation of ibuprofen compared with acetaminophen caplets. METHODS: This double-blind, randomized, parallel group study evaluated 154 subjects taking a single dose of solubilized ibuprofen, 400 mg; acetaminophen, 1000 mg; or placebo for the relief of episodic tension-type headache. Time to relief was measured using a stopwatch, and overall efficacy was measured using traditional categorical pain and relief scales. RESULTS: Ibuprofen capsules (liquigel), 400 mg, were significantly faster than both acetaminophen, 1000 mg, and placebo for all time-to-relief measures. Ibuprofen liquigel had a median time to first perceptible pain relief of 39 minutes compared with 47 minutes for acetaminophen and 113 minutes for placebo. For median time to meaningful relief, ibuprofen liquigel had a time of 39 minutes compared with 53 minutes for acetaminophen and more than 180 minutes for placebo (P</=.02 for both measures). In addition, ibuprofen liquigels demonstrated significantly superior overall analgesic efficacy compared with acetaminophen, 1000 mg, for the relief of episodic tension-type headache. Both active treatments had a side effect profile similar to placebo. CONCLUSIONS: Although several other studies have demonstrated the overall analgesic superiority of ibuprofen to acetaminophen, this study demonstrated that the liquigel formulation also provides a clinically relevant advantage for time to analgesic effects.

Absorption↗

Axillary vein thrombosis during pregnancy in association with a lupus anticoagulant.

A 42-year-old multiparous pregnant woman presented with swelling and pain of the left arm at 34 weeks gestation. She had no discoloration of her arm nor a loss of radial pulse. Duplex scanning demonstrated a thrombosis in the axillary vein. She was found to have a positive circulating lupus anticoagulant. Intravenous heparin was administered and resulted in resolution of discomfort and swelling on day four of therapy. The patient was maintained on therapeutic doses of subcutaneous heparin until vaginal delivery at 39 weeks. Prenatal course was complicated by a resolving infection believed to be due to cat-scratch disease which produced a five centimeter cystic lesion in the left axillae which was removed in the first trimester. Titers for cat-scratch disease were positive for mother and infant at delivery but infant titers were negative at six weeks. Axillary vein thrombosis in pregnancy can be complicated by pulmonary embolism and should be treated by heparin.

Adult↗