Estrogen replacement therapy in combination with continuous intrauterine progestin administration reduces the amount of circulating oxidized LDL in postmenopausal women: dependence on the dose of progestin

BACKGROUND. Oxidized low density lipoprotein (LDL) plays a key role in processes leading to atherosclerosis. Recent studies show that LDL oxidation in vitro is effectively prevented by estrogen. Yet, the effect of hormonal therapy (HT) on in vivo LDL oxidation has remained open.

AIM. We used a novel methodology for the measurement of oxidized LDL in vivo in order to investigate the effects of HT.

METHODS. The subjects were derived from two separate trials. In trial 1 (24 months) women (n?=?32) used intrauterine system releasing 10?μg/day levonorgestrel, and 2?mg oral estradiol. Trial 2 (12 months) consisted of two groups of subjects. One group (n?=?30) used an intrauterine system releasing 20?μg/day levonorgestrel, and 2?mg estradiol; the other group (n?=?32) received orally a combination of 1?mg norethisterone acetate and 2?mg estradiol. Blood samples were taken at 6 months intervals. Estimation of in vivo LDL oxidation was based on determination of baseline diene conjugation in isolated LDL.

RESULTS. Hormonal therapy in trial 1 decreased markedly in vivo LDL oxidation. The effect was seen after 6 months' HT and became more pronounced towards the end of study (41% decrease; P?<?0.0001). Contrary to this, in trial 2 the two different kinds of hormonal therapy schemes did not affect in vivo LDL oxidation.

CONCLUSIONS. The strong effect seen in trial 1 shows that intrauterine levonorgestrel with 2?mg estradiol can lower LDL oxidation in vivo. The results show that this effect depends on dosage of the progestin.     

Left-side dominance of upper extremity fracture in children

In 148 children who had sustained trauma to the upper extremities from falls, fractures were twice as common on the left as on the right side. This seemed to be due to the childrens' preferential use of the left hand to parry the fall even when both hands were free and because the left arm seemed to be more easily broken than the right arm during trauma.     

H2 receptor-mediated facilitation and H3 receptor-mediated inhibition of noradrenaline release in the guinea-pig brain

The effect of histamine and related drugs on the tritium overflow evoked electrically (0.3 Hz) or by introduction of Ca²⁺ ions into Ca²⁺-free K⁺-rich (25 mmol/l) medium containing tetrodotoxin was studied in superfused guinea-pig brain cortex, cerebellum, hippocampus or hypothalamus slices and in mouse brain cortex slices preincubated with ³H-noradrenaline. The electrically evoked tritium overflow in guinea-pig cortex slices was inhibited by histamine; the H₃ receptor antagonist clobenpropit reversed the effect of histamine to a slight facilitation. The facilitatory effect of histamine (obtained in the presence of clobenpropit) was not affected by the H₁ receptor antagonist mepyramine but abolished by the H₂ receptor antagonist ranitidine. In the absence of clobenpropit, ranitidine augmented the inhibitory effect of histamine. In slices superfused in the presence of ranitidine, the evoked overflow was inhibited by histamine and, more potently, by the H₃ receptor agonist R-α-methylhistamine in a concentration-dependent manner (maximum inhibitory effect obtained for both agonists 30–35%). The concentration-response curve of histamine was shifted to the right by the H₃ receptor antagonist thioperamide. R-α-Methylhistamine inhibited the electrically evoked tritium overflow also in guinea-pig cerebellar, hippocampal and hypothalamic slices. In cortex slices superfused in the presence of clobenpropit, the H₂ receptor agonists impromidine and, less potently, R-sopromidine facilitated the evoked overflow in a concentration-dependent manner. S-Sopromidine only tended to increase the evoked overflow. The effect of impromidine was counteracted by the H₂ receptor antagonists ranitidine and cimetidine. The extent of the maximum facilitatory effect of impromidine (by 15–20%) was about the same when (i) the Ca²⁺ concentration in the medium was reduced from 1.3 to 0.98 mmol/l, (ii) the time of exposure to impromidine was reduced from 28 to 8 min or (iii) cerebellar, hippocampal or hypothalamic slices were used instead of cortical slices. The Ca²⁺-induced tritium overflow in guinea-pig cortex slices was inhibited by histamine (in the presence of ranitidine); this effect was abolished by clobenpropit. In slices superfused in the presence of clobenpropit, impromidine failed to facilitate the Ca²⁺-evoked tritium overflow. The electrically evoked tritium overflow in mouse brain cortex slices was inhibited by histamine by about 60% (both in the absence or presence of ranitidine). The inhibitory effect of histamine was abolished (but not reversed) by clobenpropit. In conclusion, noradrenaline release in the guinea-pig brain cortex is inhibited via presynaptic H₃ receptors and facilitated via H₂ receptors not located presynaptically. In the mouse brain cortex, only inhibitory H₃ receptors occur. The extent of the H₃ receptor-mediated effect is more marked in the mouse than in the guinea-pig brain cortex. Received: 25 September 1997 / Accepted: 17 November 1997     

Tissue distribution of fentanyl and alfentanil in the rat cannot be described by a blood flow limited model

Traditionally, physiological pharmacokinetic models assume that arterial blood flow to tissue is the rate-limiting step in the transfer of drug into tissue parenchyma. When this assumption is made the tissue can be described as a well-stirred single compartment. This study presents the tissue washout concentration curves of the two opioid analgesics fentanyl and alfentanil after simultaneous 1-min iv infusions in the rat and explores the feasibility of characterizing their tissue pharmacokinetics, modeling each of the 12 tissues separately, by means of either a one-compartment model or a unit disposition function. The tissue and blood concentrations of the two opioids were measured by gas-liquid chromatography. The well-stirred one-compartment tissue model could reasonably predict the concentration-time course of fentanyl in the heart, pancreas, testes, muscle, and fat, and of alfentanil in the brain and heart only. In most other tissues, the initial uptake of the opioids was considerably lower than predicted by this model. The unit disposition functions of the opioids in each tissue could be estimated by nonparametric numerical deconvolution, using the arterial concentration times tissue blood flow as the input and measured tissue concentrations as the response function. The observed zero-time intercepts of the unit disposition functions were below the theoretical value of one, and were invariably lower for alfentanil than for fentanyl. These findings can be explained by the existence of diffusion barriers within the tissues and they also indicate that alfentanil is less efficiently extracted by the tissue parenchyma than the more lipophilic compound fentanyl. The individual unit disposition functions obtained for fentanyl and alfentanil in 12 rat tissues provide a starting point for the development of models of intratissue kinetics of these opioids. These submodels can then be assembled into full physiological models of drug disposition.Supported in part by the National Institute on Aging, RO1-AG-4594, the Anesthesia/ Pharmacology Research Foundation, and a travel grant from Janssen Pharma AB (Sweden).     

Die Genauigkeit der klinischen Untersuchung bei der Diagnose der rektalen Invagination

Ziel:   

Diese Studie wurde durchgeführt, um die routinemäßige klinische Untersuchung und die Defäkographie in der Diagnose der rektalen Invagination bei obstipierten Patienten zu vergleichen und um die Beziehungen zwischen rektaler Invagination und Symptomen zu untersuchen.     

Factor analysis and reduction of a Fear Survey Schedule among dental phobic patients

A fear survey instrument, based on the Fear Survey Schedule-II and five additional fear items, was administered to 109 patients (70 women and 39 men) on a waiting list at a specialized dental fear clinic. The fear survey was analyzed to identify its factorial structure. Five fear factors, explaining 54% of the total variance, were identified concerning areas of "illness and death", "failures and embarrassment", "social situations", "physical injuries", and "animals and natural phenomena". An ad hoc reduction of items was carried out to form a shorter, more practical to use questionnaire, which resulted in factors of four or five items with loadings greater than 0.50. The factors intercorrelated significantly (r_p varying between 0.33 and 0.59) and "illness and death" correlated highly with "physical injuries" (r_p=0.59) and "animals and natural phenomena" (r_p=0.56), while "failures and embarrassment" correlated highly to "social situations" (r_p= 0.54). Statistically significant, but generally lower correlations were found between each factor and the dental fear measures. The highest correlations were found between fear of "physical injuries" and dental fear. There was also a high and significant correlation between sex and fear of "animals and natural phenomena".