Preliminary analysis of a randomized comparison of 5-fluorouracil versus 5-fluorouracil and high-dose continuous-infusion folinic acid in disseminated colorectal cancer

In this study, 50 patients were randomly assigned to treatment with 5-fluorouracil (FUra) or FUra plus high-dose continuous-infusion folinic acid. Five of 27 evaluable patients in the FUra group versus 10 of 21 patients in the FUra plus folinic acid arm of the study had objective partial remissions, P = 0.02. Time to progression was 3.9 months for FUra and 8.0 months for FUra and folinic acid, P = 0.006; however, median survivals (11.9 versus 14.5 months) were not different in this crossover study. Toxicity in both treatment arms was mild, although patients receiving FUra plus folinic acid experienced significantly more stomatitis than patients treated with FUra alone. This study suggests that high-dose, continuous-infusion folinic acid, which produces a steady-state level of biologically active folates of 10 microM, significantly increases the therapeutic activity of FUra.     

Newer emergency reperfusion techniques in acute myocardial infarction

We have given an overview of the management of the acute myocardial infarction patient utilizing the aggressive reperfusion techniques available today. Anatomic reperfusion rates have been over 95% with the combined methods described. The remaining problems technically are those of earlier reperfusion, methods to enhance myocardial recovery after ischemia, and prevention of restenosis or reocclusion. The use of laser methodology, coronary sinus retroperfusion, partial left heart bypass, and other innovative strategies may improve these results. The introduction of tissue plasminogen activator will affect our approach and will profoundly alter society's expectations of therapeutic success. Still, patients will die from acute myocardial infarction and its complications. The search for a prevention must, therefore, not be overshadowed by our current enthusiasm for reperfusion techniques. Hopefully, our current approach will become a historical footnote as breakthroughs in preventive strategies occur.     

Deferred treatment for prostate cancer

The clinical outcome of 278 prostate cancer patients managed by a deferred treatment policy was analysed retrospectively. Following TURP or biopsy, all patients were asymptomatic and deemed suitable for management by a deferred treatment policy, i.e. hormone therapy or other forms of treatment were only initiated if and when symptomatic progression occurred. The overall 5-year survival rate was 30%; 18% of patients died from other causes without needing treatment for their prostate cancer; 11% were alive and untreated after 5 years' follow-up; 17% died from prostate cancer without further treatment. Poor tumour grade, anaemia, metastatic disease, a short history, presentation with retention, and a raised serum creatinine at presentation were associated with a poor prognosis.     

Ablation of the olfactory bulb up-regulates the rate of neurogenesis and induces precocious cell death in olfactory epithelium.

Young adult rats were unilaterally bulbectomized and tritiated thymidine ([3H]TdR) was injected at variable times following surgery to determine the effect of bulbectomy on the rates of cell proliferation and cell death in the olfactory epithelium. Removal of the olfactory bulb elicits a two- to fourfold increase in the proliferation rate of ipsilateral olfactory epithelial cells 7-50 days following surgery. On the contralateral side, there was a temporary twofold increase in the proliferation rate during the second week after surgery, but this returned to control values at 3 weeks. This temporary increase was in parallel with the response on the ipsilateral side so that the ratio between operated and unoperated sides remained at two. Cell death in olfactory epithelium is also up-regulated following bulbectomy. Death of cells can occur as early as 1 day following incorporation of [3H]TdR, i.e., well before the sensory neurons become mature. This means there is an over-production of sensory cells, and they die at all stages of their life cycle. The number of cells dying is greater after bulbectomy, indicating that the overproduction of olfactory cells is more pronounced after surgery.     

Role of topical lignocaine during carotid endarterectomy.

Forty carotid endarterectomies were undertaken in 34 patients. Operations were prospectively randomized to periarterial application of either 1 per cent lignocaine (n = 19) or normal saline (n = 21), and detailed measurements taken of intraoperative pulse rate and blood pressure. Patients receiving lignocaine demonstrated a lower pulse rate, and lower systolic and mean blood pressures than those receiving placebo, with significance in relation to clamp application and shunt removal (P < 0.05). It was particularly noticeable that patients receiving lignocaine demonstrated less intraoperative variation in pulse rate and blood pressure. Topical lignocaine stabilizes pulse rate and blood pressure during carotid endarterectomy.     

“Classical” neuroendocrine peptide hormones produced by cells of the immune system

Cells of the immune system are shown to produce peptide hormones whose production was once thought to be restricted to neuroendocrine tissue. Interestingly, in some cases, very specific stimuli elicit the production of one species of neuropeptide hormone. In other instances, it appears that some peptide hormones are constitutively produced. In either situation, the various immunocyte-derived hormones have biological activity in endocrinological assays. In the present report, a review of the various neuroendocrine hormones produced by cells of the immune system is discussed.     

Hormone replacement therapy is associated with increased C-reactive protein in women with Type 2 diabetes in the Diabetes Heart Study.

AIMS: Increased levels of inflammatory biomarkers, especially C-reactive protein (CRP), are associated with increased risk for cardiovascular disease (CVD) events, such as myocardial infarction, stroke, peripheral vascular disease, and sudden cardiac death. Medical interventions that increase CRP levels, such as hormone replacement therapy (HRT) in post-menopausal women, are under increasing scrutiny. The effect of HRT on CRP levels in women with Type 2 diabetes (T2DM) is not well documented, and conflicting conclusions have been reported. The aim of this study was to determine the influence of HRT on women with diabetes in a large cross-sectional study. METHODS: Three hundred and twenty-seven post-menopausal women with T2DM from the Diabetes Heart Study participated. Current use of HRT was determined and serum CRP levels were measured using a high-sensitivity ELISA kit. Generalized estimating equation methods were used to assess the relationship of multiple clinical and lifestyle (e.g. smoking) measures on CRP levels including differences between women taking HRT (HRT+) and not taking HRT (HRT-). RESULTS: Overall serum CRP levels were strongly associated with body mass index (P < 0.0001) and age (P < 0.0001). Of the women, 243 were not using HRT and 84 were using HRT. HRT+ and HRT- women did not differ significantly in measures of clinical traits, with the exception of higher mean low-density lipoprotein cholesterol in HRT- women (P = 0.004). In all models tested, HRT+ women had significantly higher circulating CRP levels, with P-values ranging from 0.0045 to 0.010. CONCLUSIONS: In this study of serum CRP concentration as a function of HRT in women with Type 2 diabetes, there was consistent evidence for increased circulating CRP levels in women receiving oestrogen-containing HRT. Whether HRT-induced increases in CRP can account for the adverse cardiovascular effects of HRT remains to be established; however, based on these data, there is little reason to believe that diabetic women would be spared from such an effect.     

Lipid lowering therapy leads to a reduction in sodium-lithium countertransport activity.

Erythrocyte sodium-lithium countertransport (SLC) was measured in 17 patients with either combined hyperlipidaemia or hypercholesterolaemia before and after lipid lowering therapy. Before treatment SLC related to the serum triglyceride level and was increased in combined hyperlipidaemia. After treatment the SLC had returned to normal and the change in SLC was related to the change in serum triglyceride levels. Raised SLC is associated with essential hypertension but is not related to blood pressure. Therefore, the association of raised SLC with hyperlipidaemia and essential hypertension appears to have different underlying mechanisms.