Reduction by cefodizime of the pulmonary inflammatory response induced by heat-killed Streptococcus pneumoniae in mice

It has recently become apparent that overwhelming inflammatory reactions contribute to the high mortality rate associated with pneumococcal infection in immunocompetent hosts. Cefodizime (CEF) is an antibiotic that seems to be endowed with immunomodulating properties. To investigate the influence of CEF on the pulmonary inflammatory response induced by Streptococcus pneumoniae, we infected mice with repeated intranasal inoculations of 10(7) CFU of heat-killed fluorescein isothiocyanate-labeled bacteria, which are insensitive to the killing properties of the drug. CEF downregulated but did not abolish the strong polymorphonuclear leukocyte (PMN) recruitment induced by S. pneumoniae. PMN recruitment was not primarily mediated by leukotriene B4 in this model. The drug did not interfere with intrinsic mechanisms of phagocytosis by PMNs and alveolar macrophages. CEF totally abrogated the pneumococcus-induced tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) secretion in bronchoalveolar lavage fluid. The drug also prevented IL-6 release in lung homogenates and partly inhibited TNF-alpha, but it did not interfere with IL-1alpha secretion in the lungs of infected mice. The fractional and selective downregulation of inflammatory cells and cytokines by CEF suggests cell-specific and intracellular specific mechanisms of interaction of the drug. The immunomodulatory properties of CEF may help restrain excessive inflammatory reactions, thus contributing to the reported good clinical efficacy of the drug against lower respiratory tract infections.     

Lipanor treatment of atherogenic hyperlipoproteinemia

AIM: The study of the hypolipidemic efficiency, safety and tolerance of ciprofibrate (lipanor) in therapy of atherogenic hyperlipoproteinemia. MATERIALS AND METHODS: The trial included 14 hypertensive postmenopausal females, 14 patients with diabetes mellitus type II, 14 males with coronary heart disease and primary hyperlipoproteinemia (total cholesterol > 6.5 mmol/l, triglycerides < 4.5 mmol/l under low-cholesterol diet). Lipanor was given for 12 weeks in a daily single dose 100 mg in the morning. Lipids and other biochemical indices were measured in a fasting state after 1 and 3 months of lipanor treatment. RESULTS: After 1 month of lipanor treatment there was a 22-30%, 24-49% decrease in the level of low-density lipoprotein cholesterol, triglycerides, respectively. High-density lipoprotein cholesterol increased by 16%. The hypolipidemic effect of lipanor persisted for 3 months during which triglycerides continued to fall (up to 38.5%). Lipanor was well tolerated, only one patient with diabetes mellitus had hyperactivity of creatine phosphokinase manifesting with clinical symptoms (the drug was discontinued). 3 patients developed mild side effects. Alkaline phosphatase activity inhibited in all the groups by 25-41%. CONCLUSION: Lipanor is a highly effective, safe hypolipidemic drug with good tolerance. It can be recommended for correction of atherogenic hyperlipoproteinemia in patients at high risk of atherosclerosis progression.     

English teaching in the Italian medical faculties: results of a survey

BACKGROUND: Although a compulsory examination in medical English has been present in the medical degree curriculum in Italy since 1990, guidelines indicating what should be learnt and suggesting some means of overcoming the various problems this entails are still lacking. OBJECTIVE: To investigate the main features of teaching English in the Medical Faculties and enquire into how the various problems are solved in the individual English teaching units. METHOD: A questionnaire addressing the above issues was sent out to all the Italian Universities with a Medical Faculty. RESULTS: The first finding of our survey was that response was very poor: less than 30% of the survey volunteered any reply. Within the very reduced sample which responded, there was a high degree of variation among the solutions adopted, although the underlying problems were perceived to be much the same throughout Italy. CONCLUSIONS: The general objective of the English course for medicine should be more precisely defined, together with a series of specific minimum skills the student should possess to pass the final examination. A closer collaboration among the English teaching units might help to standardize these requirements, improve the quality of the teaching and hence the level of proficiency in English for the specific purpose of medical practice.     

Three unusual causes of pediatric syncope: a reaffirmation for the screening electrocardiogram

A 74-year-old patient sought treatment for visual obscuration and clinically had signs of Graves orbitopathy. Past medical history was unremarkable except for the use of antihypertensive medication. During the hospital admission, a fluorescent treponemal antibody absorption test was reactive, indicating infection with syphilis at some time in the past. Visual deterioration despite oral corticosteroid therapy prompted orbital decompression. At the time of surgery, she sustained a globe rupture. Presumably, syphilitic scleritis was responsible, in part, for scleral thinning and weakening, predisposing her to this complication. To the authors' knowledge, globe rupture has not been previously reported during orbital decompression.     

The X-linked lymphoproliferative-disease gene product SAP regulates signals induced through the co-receptor SLAM

In addition to triggering the activation of B- or T-cell antigen receptors, the binding of a ligand to its receptor at the cell surface can sometimes determine the physiological outcome of interactions between antigen-presenting cells, T and B lymphocytes. The protein SLAM (also known as CDw150), which is present on the surface of B and T cells, forms such a receptor-ligand pair as it is a self-ligand. We now show that a T-cell-specific, SLAM-associated protein (SAP), which contains an SH2 domain and a short tall, acts as an inhibitor by blocking recruitment of the SH2-domain-containing signal-transduction molecule SHP-2 to a docking site in the SLAM cytoplasmic region. The gene encoding SAP maps to the same area of the X chromosome as the locus for X-linked lymphoproliferative disease (XLP) and we found mutations in the SAP gene in three XLP patients. Absence of the inhibitor SAP in XLP patients affects T/B-cell interactions induced by SLAM, leading to an inability to control B-cell proliferation caused by Epstein-Barr virus infections.     

Induced magnetic fields as evidence for subsurface oceans in Europa and Callisto

The Galileo spacecraft has been orbiting Jupiter since 7 December 1995, and encounters one of the four galilean satellites-Io, Europa, Ganymede and Callisto-on each orbit. Initial results from the spacecraft's magnetometer have indicated that neither Europa nor Callisto have an appreciable internal magnetic field, in contrast to Ganymede and possibly Io. Here we report perturbations of the external magnetic fields (associated with Jupiter's inner magnetosphere) in the vicinity of both Europa and Callisto. We interpret these perturbations as arising from induced magnetic fields, generated by the moons in response to the periodically varying plasma environment. Electromagnetic induction requires eddy currents to flow within the moons, and our calculations show that the most probable explanation is that there are layers of significant electrical conductivity just beneath the surfaces of both moons. We argue that these conducting layers may best be explained by the presence of salty liquid-water oceans, for which there is already indirect geological evidence in the case of Europa.     

Posttraining estrogen and memory modulation

The present paper provides a review of recent research carried out in this laboratory investigating the effects of posttraining peripheral and intrahippocampal injection of estradiol on memory in rats, and estradiol-acetylcholine interactions in memory modulation. Ovariectomized rats received an eight-trial training session in a hippocampal-dependent hidden platform water maze task. Immediately following training, rats received a posttraining peripheral or intrahippocampal injection of estradiol-cyclodextrin complex or vehicle. Twenty-four hours later rats were returned to the maze for a retention test session, and latency to escape was used as a measure of memory for the previous day's training. Peripheral posttraining injection of estradiol enhances memory relative to vehicle-treated rats. Injections of estradiol given 2 h posttraining has no effect on retention, indicating a time-dependent effect of estradiol on memory storage processes. A time-dependent memory enhancing effect of posttraining intrahippocampal injections of estradiol has also been observed in both male and ovariectomized female rats. The memory enhancing effect of peripheral posttraining injection of estradiol in ovariectomized rats is blocked by a subeffective dose of the acetylcholine muscarinic receptor antagonist scopolamine, suggesting that estradiol interacts with cholinergic systems in memory modulation. Concurrent peripheral posttraining injection of a subeffective dose of estradiol and a subeffective dose of the cholinergic agonist oxotremorine produces a synergistic memory enhancing effect. The findings suggest that: (1) estradiol selectively influences memory storage independent of an effect on nonmnemonic processes, (2) the hippocampus is a potential neuroanatomical site of action mediating estrogenic effects on memory, and (3) estradiol interacts with cholinergic systems in memory modulation.     

Hemispheric contributions to the integration of visual and auditory information in speech perception

Differential hemispheric contributions to the perceptual phenomenon known as the McGurk effect were examined in normal subjects, 1 callosotomy patient, and 4 patients with intractable epilepsy. Twenty-five right-handed subjects were more likely to demonstrate an influence of a mouthed word on identification of a dubbed acoustic word when the speaker's face was lateralized to the LVF as compared with the RVF. In contrast, display of printed response alternatives in the RVF elicited a greater percentage of McGurk responses than display in the LVF. Visual field differences were absent in a group of 15 left-handed subjects. These results suggest that in right-handers, the two hemispheres may make distinct contributions to the McGurk effect. The callosotomy patient demonstrated reliable McGurk effects, but at a lower rate than the normal subjects and the epileptic control subjects. These data support the view that both the right and left hemisphere can make significant contributions to the McGurk effect.     

From ethnographic record to system design

This paper explores the issues involved in moving from ethnographic explorations of work in context to a practical contribution to system design. It does so using the example of an interdisciplinary research project involving sociologists and computer scientists in the domain of air traffic control systems. It forms a pair with another paper (Sommerville et al., 1992) exploring these questions from the perspective of our computer science partners. We characterise ethnography as a research method, and consider the differences between undertaking it for strictly sociological or anthropological purposes by contrast with interdisciplinary and design purposes. We summarise some of our results in ethnographic explications of the work of air traffic controllers, and the sociality which it manifests. We describe the dialogues involved in rendering these observations informative for systems design, and the mutual translations implied in attempting to reconcile sociological with software engineering questions about supporting the work. We conclude by specifying some features of cooperative work which an engineering approach is in danger of overlooking; the ways, and limits, in which ethnographers can form a bridge between users and designers; and some of the conflicts of interest entrained in generating technical change.The research is funded by the UK MRC/SERC/ESRC Cognitive Science/HCI Initiative with the title Social Analysis of Control Systems for HCI Design, grant number SPG 8931598. The computer science partners are Professor Ian Sommerville, Dr Tom Rodden, Dr Pete Sawyer and Mr Richard Bentley. Thanks are due to Val King, Kjeldt Schmidt, Ian Sommerville and Tom Rodden for very helpful comments on earlier drafts of this paper.