Annals of clinical research最新文献

Estrogen receptor (ER) concentration of breast cancer tissue is important in predicting the response of each patient to hormonal, especially antiestrogen treatment. About half of the patients with ER rich tumours respond and only about 10% of the patients with ER poor tumours respond to antioestrogen treatment. Tamoxifen is a well known and widely used drug. Toremifene is a new antioestrogen, developed in Finland. At standard doses both compounds have comparable hormonal and antitumour effects, and there is no clear difference between the compounds in the affinity to ER. The value of ER in predicting the response to tamoxifen and toremifene therapy in ER positive breast cancer is significant. It is not known, however, if the role of ER remains the same with high dose toremifene. Although ERs are an important predictive factor, the antioestrogens evidently act through them only in part. As the prediction is correct in about half of the patients, other mechanisms must influence tumour growth regulation, such as the expression of oncogenes and the synthesis and activity of growth factors.

The established antipsychotic drugs act mainly by antagonizing dopamine mediated synaptic transmission in the brain. Increase in the rate of production of dopamine metabolites as well as the firing rate of dopamine-containing neurons can be interpreted as compensatory responses to an interruption of synaptic transmission at dopamine nerve terminals. The demonstration of involvement of limbic and cortical mechanisms in the antipsychotic activity of neuroleptic drugs is far more difficult than the involvement of nigro-striatal and tubero-infundibular mechanisms in the neurological and neuroendocrine effects of these drugs. Application of radioreceptor techniques to dopamine research has supported the findings obtained by other neuropsychopharmacological research techniques, providing more direct evidence of dopamine receptor blockade by neuroleptic drugs. Further research is needed especially in studying the nature of the time-dependent adaptive changes at the receptor sites as well as the differences between the different dopamine projections and neural systems in the brain. The different subtypes of dopamine receptors in the brain, currently called D1 and D2 dopamine receptors, seem to be parallel, although in many respects independently-acting regulatory systems. Dopamine D2 receptor-selective antagonists such as sulpiride seem to cause selective D2 receptor up-regulation. Prolactin secretion seems to be regulated by D2 dopamine receptors. The exact physiological role of D1 dopamine receptors as well as the clinical consequences of selective D1 antagonism is not known. Sulpiride and clozapine are examples of atypical neuroleptic compounds that have quite different profile of action, the former having strong and selective antidopaminergic action, the latter combining a number of non- dopaminergic mechanisms with rather slight effects on dopamine receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Epidemiological studies have left no doubt that moderate to vigorous physical training (PT) of endurance type decreases atherogenic lipoprotein fractions and increases vasoprotective lipoproteins. Depending on the underlying metabolic abnormality in various dyslipoproteinaemias a different response to endurance training was observed. PT is particularly effective in most forms of primary hypertriglyceridaemias. PT acts on both excessive VLDL production and fractional catabolic rate of TG--rich lipoproteins. However, improved removal seems to be of dominating importance. In primary hypercholesterolaemia LDL--cholesterol levels did not change during a 4 weeks exercise regimen with standardized isocaloric lipid lowering diet. In observational studies with hyperlipidaemic patients with stable body weight and under lipid lowering diet, during the first 4-6 weeks no significant effect on HDL was seen, whereas longterm studies clearly demonstrate an increase in HDL--cholesterol. Further beneficial effects of PT in hyperlipidaemic patients are improved glucose tolerance, down--regulation of hyperinsulinaemia, lowering of blood pressure and correction of hypercoagulability of the blood.

The benzodiazepines had already been in wide use as anxiolytics and anticonvulsants for more than ten years before their site of action in the central nervous system, the benzodiazepine receptor, was discovered. Simultaneously, a binding site in the peripheral organs, e.g. heart, lungs and kidneys, was found. Although some benzodiazepines, such as diazepam, bind to both central and peripheral benzodiazepine receptors with a high affinity, these two binding sites exhibit quite different properties. It is already clear that the central benzodiazepine receptors are in many regions of the brain coupled with the receptors for gamma-amino butyric acid, and they mediate the acute actions of benzodiazepines in the central nervous system. Through them opposite effects, such as anxiety and convulsions, can also be evoked by using inverse agonists, e.g. some beta-carbolines. All these effects can be blocked with benzodiazepine receptor antagonists, some of which are already used as specific antidotes against benzodiazepine overdose. The multitude of pharmacological effects that can be produced through central benzodiazepine receptors provides a good opportunity for the development of new drugs. The role of the peripheral-type receptors is less clear, but it seems that they are connected with more slowly-appearing drug actions, such as modulation of cell proliferation. Now that endogenous ligands for both the central-type (a peptide called diazepam binding inhibitor; DBI) and for the peripheral-type (porphyrins) benzodiazepine receptors have been discovered, even more productive research can be expected.

Forty-six consecutive patients with chronic renal failure (CRF) were assessed radiographically, endoscopically and histologically for duodenal inflammation. Their gastric secretion was also examined. Thirty-eight patients with non-ulcer dyspepsia served as controls. Histologically established duodenitis was more common in CRF patients than in controls. Among the non-dialyzed patients its prevalence reached 28% (9/32), while in the controls it was 5% (2/38) (p less than 0.05). The CRF patients with duodenitis had upper GI symptoms, hypersecretion of acid (p less than 0.05) and duodenal ulcer disease (p less than 0.05) more frequently compared with the CRF subjects with normal duodenal mucosa. The correlation of radiographically and endoscopically detected duodenitis with that found microscopically was poor.

From time to time it has been claimed that the thermal stress caused by sauna bathing can be harmful to persons with cardiovascular disorders. Furthermore, elderly persons in general, who have experienced no symptoms from bathing, have also been cautioned. However, several studies carried out in Finland did not confirm the adverse effects of bathing on the elderly and cardiovascular patients. The controversial results obtained in Finnish and in some foreign studies are at least partly due to the different test conditions. The typical Finnish sauna bath is safe, and even patients who have recovered from acute myocardial infarction can enjoy the sauna without incurring any harmful cardiovascular effects.

The aesthetic pleasure of the Finnish sauna may be disturbed by an intense itch caused by sweating in a few people with atopic dermatitis. The heat of the sauna may also initiate cholinergic urticaria. The sauna itself does not cause drying of the skin although incorrect washing habits may lead to this. The use of soap is adviced especially in the anogenital region and armpits, but the use of a washing brush and sponge is not adviced. Sauna bathing facilitates the removal of hyperkeratotic scales in psoriasis, and the use of petrolatum, emollient creams or topical antipsoriatic regimens has been found to be beneficial for many patients. Dermatophytes and other infective microorganisms are easily killed by the heat of the sauna. The pleasing sensations in the skin after sauna bathing are thus only very seldom disturbed by itches or some other unpleasant consequence.