Essential thrombocythemia at diagnosis: causes of diagnostic evaluation and presence of positive diagnostic findings

Antipsychotic drugs are effective in psychoses, whatever the aetiology of the disorder. The positive symptoms tend to respond more readily. The need for developing new drugs arises from the refractoriness of the negative symptoms, the 10-25% of the patients that are treatment-resistant and the problems of short-, and long-term extrapyramidal side-effects. Thus far, five drugs differing from the classical antipsychotics have been licensed for use: clozapine, olanzepine, risperidone, sertindole and sulpiride, and in at least some European countries quetiapine is now in the final phase of clinical research. This review starts with a brief introduction to symptomatology, is limited to the registered drugs and addresses differences with the classical drugs in pharmacology, pharmacokinetics, clinical aspects and side-effects. Clozapine, risperidone and sulpiride can be considered for clinical use in refractory patients, and these three together with olanzapine and sertindole are candidates when extrapyramidal side-effects cause a clinical problem.     

Oxidized LDL promotes vascular endothelial cell pinocytosis via a prooxidation mechanism

Human low density lipoprotein (LDL) is prepared in the presence of antioxidants and is oxidized to different levels (measured by thiobarbituric acid reactive substance) with copper ion. The effects of unoxidized LDL and oxidized LDL (ox-LDL) on stress fiber formation, cell membrane ruffling, and pinocytosis (measured by [14C]sucrose uptake) in cultured human umbilical cord vein endothelial cells (EC) are compared. We show that at a concentration range of 100 to 200 microg cholesterol/ml, both unoxidized LDL and ox-LDL promote EC elongation and stress fiber formation, but the effect by the latter is more prominent when compared at the same dose range. In addition, ox-LDL also induces EC membrane ruffling and promotes pinocytosis. These effects are positively correlated with the extent of LDL oxidation and depend on the dose of ox-LDL. Ox-LDL-promoted membrane ruffling and pinocytosis are effectively blocked by brief preexposure of the cells to antioxidants. In contrast, stress fiber formation is not affected by antioxidant pretreatment. Although unoxidized LDL also promotes [14C]sucrose uptake, it is less potent than ox-LDL and significantly higher concentrations are required to produce a detectable effect. Unlike ox-LDL, unoxidized LDL-enhanced pinocytosis is not accompanied by the appearance of membrane ruffling; therefore, they may act via different mechanisms. Elevated pinocytosis may increase transcytotic activity of the endothelium, leading to an increased influx of plasma components such as LDL into the subendothelial space.     

The delayed anovulation syndrome: influence of hormones and correlation with behaviour

Experiments were conducted to assess the influence of the ovary and various steroid treatments on the development of the delayed anovulatory syndrome (DAS) in female rats. The influence of neonatally administered androgen on the development of ovarian function and female sexual behaviour was studied. It was found that neither the presence of the ovary nor the administration of oestrogen or androgen affected the time-course of the DAS. Doses of androgen which produced the DAS had little effect on female sexual behaviour and there was no evidence of time-dependent changes in sexual behaviour comparable to the time-dependent changes of ovarian physiology observed during the DAS.     

The value of baseline chest radiograph reports in the care of elderly patients in an emergency department

The authors used a before/after research design to determine the impact of written reports of baseline chest radiographs (CXRs) on the care of elderly patients during 48 emergency department visits. Internal medicine housestaff completed questionnaires that included inquiries about their treatment plans for the patients both before and after they reviewed reports of baseline CXR results. The investigators compared these answers to determine the proportion of patients for whom baseline CXR reports changed patient management. In addition, three faculty reviewers used the nominal group process, a consensus analysis approach, to measure treatment changes and to estimate benefit to the patients from the alterations in management. The housestaff indicated that written baseline CXR reports caused them to change treatment plans during only 2 (4%) of the 48 visits. In both cases, they provided aggressive treatment for congestive heart failure because of baseline CXR results. The faculty reviewers could find only one case in which baseline CXR findings might have changed their management plans. Moreover, they were not convinced that the treatment changes indicated by the housestaff actually benefitted the patients. These results suggest that written reports of baseline CXRs do not improve the care of acutely ill patients in an emergency department setting.     

Auditory suppression and frequency selectivity in older and younger adults

Age differences in auditory suppression were examined by comparing auditory-filter shapes obtained with simultaneous and forward masking at 2 kHz in young and elderly normal-hearing listeners. To compensate for the decay of forward masking, growth of masking functions were used to transform thresholds obtained with a notched-noise masker to the level of a continuous noise band that would give the same threshold values. Although both age groups exhibited smaller equivalent rectangular bandwidths (ERBs) when the filters derived from transformed thresholds were obtained with forward masking, the change from simultaneous to nonsimultaneous masking was significantly greater for young adults. Measures of the low- (Pl) and high- (Pu) frequency sides of the filters for young listeners indicated that the slopes of both sides increased following a change from simultaneous to forward masking but that the high-frequency side exhibited significantly greater sharpening. Filter slopes (both upper and lower) for older adults, in contrast, did not differ between the two masking procedures. The findings from the study are discussed as reflecting possible age differences in auditory suppression. However, it is also noted that conclusions regarding differences between filter shapes derived with simultaneous and forward masking are limited to filter parameters determined with transformed (as described above) thresholds.     

Stimulation of gluconeogenesis with 1,3-butanediol in the perfused rat liver

An intensified synthesis of glucose is observed in gluconeogenesis from endogenous precursor only for the first 30 min of perfusion. Pyruvate introduction into the medium raises phosphoenolpyruvate carboxykinase and fructose-1,6-diphosphatase activities in the liver and determines maintenance of the glucose formation high rate for 90 min of perfusion. 1,3-butanediol is found to have a stimulating effect on gluconeogenesis from pyruvate. Introduction of 1,3 bytanediol into perfusate decreases the redox state of free NAD-pairs, increases the content of phosphoenolpyruvate, malate. ATP and the phosphoenolpyruvate carboxykinase and fructose-1.6-diphosphatase activity in the perfused liver.