Accumulation of chylomicron remnants in homozygous subjects with familial hypercholesterolaemia

Despite the obvious differences between the USA and UK health care systems, they share the characteristics of being motivated and managed in relation to cost and process rather than quality (the improved health status of patients). Whilst governments and insurers across the world use the rhetoric of quality, they, as epitomized by the behaviours of UK and USA decision makers, fail to define, measure and implement quality outcome policies. These behaviours are examined and some of their causes are explored briefly. Competition, as designed and used in public (e.g. UK National Health Service) and private (e.g. USA managed care) markets is shown to fail both to identify quality outcome targets and to provide evidence-based and efficient mechanisms to motivate decision makers to be orientated towards continuous quality outcome improvement in health care. A central policy challenge is, consequently, not just the measurement of quality outcomes but also their management into practice.     

Mathematical models for motile bacterial transport in cylindrical tubes

Mathematical models considering motile bacterial transport within a geometrically restrictive cylindrical tube were developed. Two macroscopic transport parameters, the random motility coefficient as a self-diffusion coefficient of the cell population and the chemotactic velocity as a chemical-induced velocity, were derived. The three-dimensional cell balance equation was reduced to forms similar to Segel's one-dimensional phenomenological cell balance equations with additional modifications for bacteria-wall interactions. Two conceptually different approaches accounting for such interactions were presented. The first approach parallels treatments in the gas kinetic theory by viewing bacterial interactions with walls as collisions and subsequent diffusive/specular reflections, which led to the Bosanquet formula for the bacterial diffusion coefficient. Based on the experimental observation that bacterial swimming motion is guided by a straight tube, the second approach considered modifications in the bacterial swimming orientation as a consequence of various long-range interactions with the tube surface. A phenomenological turning model capable of aligning bacterial motion along a tube axis was proposed. The model predicts that under the geometrical restriction of a small cylindrical tube, the macroscopic bacterial transport resulting from the proposed turning model can exhibit behavior that ranges from dimensionally reduced diffusion to pure wave propagation, depending on the influence of the tube diameter on the reversal probability in the bacterial swimming motion. Our theoretical model provides explicit equations that explain how such a transition can occur. The predicted results were then qualitatively compared with experimental data from the literature. As a preliminary comparison, we concluded that bacterial transport in cylindrical tubes of diameter 10 micrometers remains in the mode of a dimensionally reduced diffusion, and shifts to a wave motion when the tube diameter decreases to 6 micrometers.     

A PC-based software test for measuring alcohol and drug effects in human subjects

A new software-based visual search and divided-attention test of cognitive performance was developed and evaluated in an alcohol dose-response study with 24 human subjects aged 21-62 years. The test used language-free, color, graphic displays to represent the visuospatial demands of driving. Cognitive demands were increased over previous hardware-based tests, and the motor skills required for the test involved minimal eye movements and eye-hand coordination. Repeated performance on the test was evaluated with a latin-square design by using a placebo and two alcohol doses, low (0.48 g/kg/LBM) and moderate (0.72 g/kg/LBM). The data on 7 females and 17 males yielded significant falling and rising impairment effects coincident with moderate rising and falling breath alcohol levels (mean peak BrALs = 0.045 g/dl and 0.079 g/dl). None of the subjects reported eye-strain or psychomotor fatigue as compared with previous tests. The high sensitivity/variance relative to use in basic and applied research, and worksite fitness-for-duty testing, was discussed. The most distinct advantage of a software-based test that operates on readily available PCs is that it can be widely distributed to researchers with a common reference to compare a variety of alcohol and drug effects.     

Adjuvant chemotherapy for patients with resected Dukes' C and high-risk B2 colon cancer with fluorouracil and levamisole

Carcinoma of the large bowel is the second leading cause of cancer mortality in Singapore. Although the great majority of patients are discovered at a stage where resection with curative intent is possible, almost half of the patients afflicted will die of it. The combination of 5-fluorouracil + levamisole used in patients with curatively resected high risk Dukes B2 and all Dukes' C colon cancers has been shown to reduce cancer recurrence rate and improve overall survival. Since 1990 adjuvant chemotherapy has been recommended for this group of patients. This report describes patients treated in Singapore, their toxicities and their outcome. A total of 341 patients were treated between 1990 and 1996. Treatment compliance was 71.8%. Toxicity was moderate with mainly grade 1-2 nausea and vomiting, diarrhoea, stomatitis, alopecia, and neutropenia. There was 1 treatment-related death. Median recurrence-free interval was 81 months and median survival was not reached at 90 months. This regimen is tolerable. Until further randomised reports comparing 5-fluorouracil + levamisole to other combinations are available, this combination chemotherapy is recommended to patients after surgical resection of the high risk Dukes' B2 and Dukes' C colon cancer to reduce cancer recurrence and improve overall survival.     

Synthesis and pharmacological evaluation of new flosulide analogues, synthesized from natural safrole

OBJECTIVE: To study the effect of adjuvant chemotherapy after curative hepatic resection in patients with hepatocellular carcinoma. DESIGN: A randomized controlled trial. SETTING: A tertiary referral center. PATIENTS: During a 54-month period, 142 patients with hepatocellular carcinoma underwent hepatic resection at 1 institution. Sixty-six patients who survived the operation and had no demonstrable evidence of residual disease on ultrasonographic examination and hepatic angiographic testing at 1 month after surgery agreed to participate in the study. The median follow-up time was 28.3 months. INTERVENTION: Thirty patients received a combination of intravenous epirubicin hydrochloride (8 doses of 40 mg/m2 each at 6-week intervals) and transarterial chemotherapy using an emulsion of iodized oil and cisplatin (3 courses with a maximum dose of 20 mL each at 2-month intervals). Thirty-six patients had no adjuvant treatment. MAIN OUTCOME MEASURES: Recurrence rate and disease-free survival. RESULTS: A total of 138 courses of intravenous epirubicin was given to the 30 patients. Sixty-one courses of transarterial chemotherapy were given to only 29 of the 30 patients assigned to the treatment group, because the hepatic artery in 1 patient was thrombosed. Six patients (20%) had chemotherapy-related complications with no mortality. Twenty-three of 30 patients in the treatment group and 17 of 36 patients in the control group had recurrences (P=.01). Patients who received adjuvant chemotherapy had a higher incidence of extrahepatic metastases (11 patients vs 5 patients; P=.03). The respective disease-free survival rates at 1, 2, and 3 years were 50%,36%, and 18% for the treatment group and 69%, 53%, and 48% for the control group (P=.04). CONCLUSION: In a group of patients who underwent curative resection of hepatocellular carcinoma, postoperative adjuvant chemotherapy using the present regimen was associated with more frequent extrahepatic recurrences and a worse outcome.     

The role of glycoproteins in neural development function, and disease

Glycoproteins play key roles in the development, structuring, and subsequent functioning of the nervous system. However, the complex glycosylation process is a critical component in the biosynthesis of CNS glycoproteins that may be susceptible to the actions of toxicological agents or may be altered by genetic defects. This review will provide an outline of the complexity of this glycosylation process and of some of the key neural glycoproteins that play particular roles in neural development and in synaptic plasticity in the mature CNS. Finally, the potential of glycoproteins as targets for CNS disorders will be discussed.