Methodology and early findings of the Diabetes Management Project: a cohort study investigating the barriers to optimal diabetes care in diabetic patients with and without diabetic retinopathy

Background: The Diabetes Management Project is investigating the clinical, behavioural and psychosocial barriers to optimal diabetes care in individuals with and without diabetic retinopathy. Design: Prospective cohort. Participants: Two hundred and twenty‐three and 374 patients without and with diabetic retinopathy, respectively. Methods: All individuals underwent a comprehensive dilated eye test, anthropometric measurements, blood and urine samples, and psychosocial questionnaires. Main Outcome Measures: Good glycaemic control was defined as glycosylated haemoglobin < 7%, good blood pressure control as systolic and diastolic values ≤130 and 80 mmHg, respectively, and good diabetes control as glycosylated haemoglobin < 7% and blood pressure values ≤130 and 80 mmHg. Results: Four hundred and one males (65.4%) and 212 females (34.6%) aged 26–90 years (mean age ± standard deviation = 64.6 ± 11.6) were examined. The median glycosylated haemoglobin for all participants was 7.5% (interquartile range = 1.7%). Average systolic and diastolic blood pressure values were 139.7 mmHg (standard deviation = 18.8) and 92.7 mmHg (standard deviation = 30.9), respectively. Initial data analyses indicate that over two‐thirds of participants with diabetes have poor glycaemic control, which was worse in those with diabetic retinopathy compared with those without (76.3% vs. 49.3%; P < 0.001). Blood pressure control was similar for those with and without diabetic retinopathy, with almost a third (28.5%) of the total sample having poor blood pressure control. Overall, those with diabetic retinopathy had poorer diabetes control than those without (24.3% vs. 13.7%; P = 0.002). Conclusions: Our findings substantiate the implementation of the Diabetes Management Project, developed to assess factors associated with suboptimal diabetes care.     

Chemoprevention of colorectal cancer

Colorectal cancer is the third most incident cancer in the United States and is second only to lung cancer as a cause of cancer-related mortality. Colorectal cancer develops through a multistep process characterized by histopathological precursor lesions and molecular genetic alterations. This sequential process of tumorigenesis provides opportunities for the development and testing of both primary and secondary prevention strategies. This review focuses on chemoprevention, which is defined as the use of natural or synthetic agents to reverse the process of carcinogenesis. Epidemiological studies have consistently shown that chronic intake of nonsteroidal anti-inflammatory drugs (NSAIDs), principally aspirin, can reduce the incidence of colorectal adenomas and carcinomas. Evaluation of NSAIDs, including newer selective cyclo-oxygenase-2 inhibitors, in carcinogen-induced and genetically manipulated animal models of colorectal cancer demonstrates that these drugs are effective chemopreventive agents. In humans, the NSAID sulindac has been studied in familial adenomatous polyposis patients and was found to regress colorectal adenomas in a placebo-controlled trial. More recently, the selective cyclo-oxygenase-2 inhibitor Celebrex was also shown to be effective in familial adenomatous polyposis and was approved by the Food and Drug Administration as a adjuct to usual care in these patients. NSAIDs, as well as other chemopreventive agents, are currently being studied in patients at increased risk of colorectal cancer, including those with sporadic adenomas. The outcome of these studies has the potential to impact patient management practices. However, chemopreventive agents cannot be recommeded at present for average-risk individuals or for those with sporadic colorectal neoplasia. In addition to demonstrating efficacy, chemopreventive agents must be safe and well tolerated for chronic administration and should be relatively cost-effective. Although still in its infancy, the field of chemoprevention is an exciting and rapidly advancing area of investigation. Chemopreventive strategies, if effective, offer the promise of producing a paradigm shift in our current approach to colorectal cancer.     

The cloning and sequencing of thealcB gene,coding for alcohol dehydrogenase II,inAspergillus nidulans

Alcohol dehydrogenase II (ADH II, structural genealcB) was purified from a strain H1035,biA1; alcE1; alc500 alcD1, which produces 100-times more ADH II activity than thealcAalcR deletion strain (alc500). Antibodies were raised against this ADH, and were used to screen a cDNA library in gt11. We have isolated the gene for an ADH which is over-expressed in H1035, and which we believe to be thealcB gene; cDNA and genomic clones were sequenced. The sequence contains three introns and encodes a protein of 367 amino acids. This protein shows a clear level of identity to a range of alcohol dehydrogenases, but is no more closely related to the ADH I and ADH III previously described inA. nidulans than to the ADHs ofS. pombe andS. cerevisiae. The significance of consensus sequences found in the 5 region of the gene is discussed in relation to the regulation of the gene.     

Acetylcholinesterase activity and acetylcholine effects in the cerebello-rubro-thalamic pathway of the cat

Unilateral transections of the brachium conjunctivum (BC) of cats resulted, after 2–3 weeks, in marked loss of acetylcholinesterase (AChE) activity from the contralateral red nucleus (RN) and ventral tier nuclei of the thalamus (VA-VL). Significant changes in activity were not observed in other locations. Sensitivity of RN neurons to iontophoretically applied acetylcholine (ACh) was studied under conditions which should maximize ACh sensitivity, including AChE inhibition, but ACh was found to have only a weak depressant effect on excitability or no effect at all. Intravenous physostigmine usually increased spontaneous activity of RN neurons, and sometimes increased potentials evoked by electrical stimulation of cerebellar nuclei, to a small extent. Anticholinergic drugs were found not to influence such evoked responses, except to reverse the effects of physostigmine. It is concluded that ACh is not a major transmitter in the excitatory cerebello-rubral tract in spite of the relationship of AChE to this pathway.