Antiphospholipid antibodies: are they pro-atherogenic or an epiphenomenon of atherosclerosis?

Antiphospholipid antibodies are the hallmark of the antiphospholipid syndrome which is characterized by thrombosis. There are currently data supporting an association between these autoantibodies and atherosclerosis as well. Human studies suggest that anti-cardiolipin and anti-beta2-glycoprotein-I antibodies are elevated in patients having coronary artery disease compared with controls. Anti-cardiolipin antibodies are also associated with typical chest pain, significant coronary artery stenosis on angiography and prediction of myocardial infarction. Laboratory studies and murine models support the pro-atherogenic role of these autoantibodies, as they are involved in uptake of oxidized LDL into macrophages, and immunization of mice with them results in enhanced atherosclerosis. There is some evidence that high anti-beta2-glycoprotein-I antibodies can present a risk factor for atherosclerosis, but more epidemiological data are required in order to confirm whether the pro-atherogenic properties of anti-phospholipid antibodies signifies an independent risk factor for atherosclerosis and its complications.     

Phenotypes of childhood asthma: are they real?

It has been suggested that there are several distinct phenotypes of childhood asthma or childhood wheezing. Here, we review the research relating to these phenotypes, with a focus on the methods used to define and validate them. Childhood wheezing disorders manifest themselves in a range of observable (phenotypic) features such as lung function, bronchial responsiveness, atopy and a highly variable time course (prognosis). The underlying causes are not sufficiently understood to define disease entities based on aetiology. Nevertheless, there is a need for a classification that would (i) facilitate research into aetiology and pathophysiology, (ii) allow targeted treatment and preventive measures and (iii) improve the prediction of long‐term outcome. Classical attempts to define phenotypes have been one‐dimensional, relying on few or single features such as triggers (exclusive viral wheeze vs. multiple trigger wheeze) or time course (early transient wheeze, persistent and late onset wheeze). These definitions are simple but essentially subjective. Recently, a multi‐dimensional approach has been adopted. This approach is based on a wide range of features and relies on multivariate methods such as cluster or latent class analysis. Phenotypes identified in this manner are more complex but arguably more objective. Although phenotypes have an undisputed standing in current research on childhood asthma and wheezing, there is confusion about the meaning of the term ‘phenotype’ causing much circular debate. If phenotypes are meant to represent ‘real’ underlying disease entities rather than superficial features, there is a need for validation and harmonization of definitions. The multi‐dimensional approach allows validation by replication across different populations and may contribute to a more reliable classification of childhood wheezing disorders and to improved precision of research relying on phenotype recognition, particularly in genetics. Ultimately, the underlying pathophysiology and aetiology will need to be understood to properly characterize the diseases causing recurrent wheeze in children. Cite this as: B. D. Spycher, M. Silverman and C. E. Kuehni, Clinical & Experimental Allergy, 2010 (40) 1130–1141.     

Changes of sleep EEG slow-wave activity in response to sleep manipulations: to what extent are they related to changes in REM sleep latency?

SUMMARY  Sleep interventions may have direct effects on slow-wave activity (SWA, i.e. power of the sleep EEG signal in the 0.75-4.5 Hz range) as well as indirect ones caused by changes in REM sleep (REMS) latency. The effects of changes in REMS latency on SWA were investigated by analysing simulations with a mathematical model. Mean SWA in the first non-REMS episode shows an initial increase and a later decline as a function of REMS latency. In the second non-REMS episode, mean SWA decreases with increasing REMS latency. These results of the simulations were validated with experimental data.
In the evaluation of the effects of sleep interventions on SWA the effects of the timing of REMS have to be accounted for. The analysis of SWA over a sufficiently long constant amount of time spent in non-REMS proves to be relatively independent of REMS latency, which allows conclusions about the effects of sleep interventions on SWA per se.     

Neurological soft signs in schizophrenia: are they related to negative or positive symptoms, neuropsychological performance, and violence?

This investigation was carried out on 31 unemployed schizophrenic outpatient men. The general purpose was to explore new aspects of neurological soft signs in schizophrenia. A 108-item version of the Nathan Kline Institute scale of soft signs, the Schedule for Affective Disorders and Schizophrenia psychiatric interview, the negative and positive symptom scale (PANSS), a comprehensive scale of life-time history of violence, and a large set of neuropsychological tests were administered. It was found that "motor" soft signs were significantly more prevalent than "sensory-perceptual" signs, but that each body side manifested equal numbers of neurological signs. Before and after statistical correction for age, education, alcoholism, drug abuse disorder, and daily and cumulative neuroleptic dosage, orbitofrontal-type neuropsychological tasks measuring "impulsivity" related very robustly to the soft signs. Furthermore, before and after the same statistical corrections, right body-side signs correlated significantly with the same neuropsychological tests, whereas left body-side signs did not. The PANSS scores and levels of lifetime violence generally did not correlate significantly with neurological soft signs. The latter negative findings, we think relate to the fact that these were relatively high-functioning (i.e., outpatient) schizophrenics. Overall, the results support notions of frontal lobe and left hemisphere involvement in schizophrenia, these two dysfunctional systems being apparently linked at the level of the orbitofrontal area of the brain.     

Asbestos fibres in drinking water: are they carcinogenic or not?

The paper discusses the possibility of a carcinogenic effect of consuming drinking water contaminated by asbestos fibres.     

The cysteinyl leukotrienes: where do they come from? What are they? Where are they going?

Cysteinyl leukotrienes are established mediators of bronchial asthma and have agonist roles analogous to those of histamine in allergic rhinitis. We now know that the substance originally termed slow-reacting substance of anaphylaxis was composed of three cysteinyl leukotrienes that act in the inflammatory response via receptors on smooth muscle and on bone marrow-derived inflammatory cells. K. Frank Austen describes the work culminating in the identification, biosynthesis and functional characterization of these moieties.     

Risks of infection in xenotransplantation: what are they and how are they to be controlled?

Porcine grafts are a potential source of pathogenic agents capable of contaminating the recipient. The spread of porcine retroviruses in the patient's tissues is a major risk that must be rigorously evaluated. The control of the microbiological state of the pig donor, concerning retroviruses and other pathogens, is the necessary condition for controlling this risk.     

Hypochromic macrocytes: are they reticulocytes?

Automated full blood counters measuring the size and haemoglobin concentration of individual red cells by high and low angle light scatter can provide estimates of the percentage of cells which are abnormal in either or both of these variables. The hypothesis that an increase in the number of large cells with a reduced haemoglobin content ("hypochromic macrocytes") was indicative of a reticulocytosis was investigated. A correlation was shown between the percentage of hypochromic macrocytes and the reticulocyte count. This correlation was too weak to allow the actual reticulocyte percentage to be predicted from the percentage of hypochromic macrocytes. An increased percentage of hypochromic macrocytes, however, often indicates an increased reticulocyte count and thus serves to chart the haematologist to this possibility.     

Gastrointestinal stromal tumors: are they of cajal cell origin?

Recently some reports have suggested that gastrointestinal stromal tumors (GIST) might originate from the interstitial cells of Cajal or differentiate into them because they express c-kit and/or CD34 and indicated that the majority of previously diagnosed smooth muscle tumors (SMT) actually belong to GIST, but are not true SMT. We, therefore, detected c-kit, CD34, SMA, and S-100 in 106 Chinese cases of gastrointestinal tumors, which were histopathologically diagnosed as smooth muscle tumors originally, to demonstrate the immunophenotypes of these tumors. The results showed that 73 cases had immunoreaction with c-kit and/or CD34, of which 48 cases showed coexpression with either SMA or S-100 or with both. A correlation between the immunophenotypes and known histopathological parameters was also shown here based on follow-up data. We suggest that the concept of GIST should not be used as an umbrella to cover all gastrointestinal mesenchymal tumors, but be defined in a narrow term as differing from true smooth muscle tumors.     

Patients with primary insomnia in the sleep laboratory: do they present with typical nights of sleep?

The validity of sleep laboratory investigations in patients with insomnia is important for researchers and clinicians. The objective of this study was to examine the first‐night effect and the reverse first‐night effect in patients with chronic primary insomnia compared with good sleeper controls. A retrospective comparison of a well‐characterised sample of 50 patients with primary insomnia and 50 good sleeper controls was conducted with respect to 2 nights of polysomnography, and subjective sleep parameters in the sleep laboratory and the home setting. When comparing the first and second sleep laboratory night, a significant first‐night effect was observed across both groups in the great majority of the investigated polysomnographic and subjective variables. However, patients with primary insomnia and good sleeper controls did not differ with respect to this effect. Regarding the comparison between the sleep laboratory nights and the home setting, unlike good sleeper controls, patients with primary insomnia reported an increased subjective sleep efficiency on both nights (in part due to a reduced bed time) and an increased subjective total sleep time on the second night. These results suggest that even the second sleep laboratory night does not necessarily provide clinicians and researchers with a representative insight into the sleep perception of patients with primary insomnia. Future studies should investigate whether these findings also hold for other patient populations.     

Glucose-sensing neurons: are they physiologically relevant?

Glucose homeostasis is of paramount concern to the brain since glucose is its primary fuel. Thus, the brain has evolved mechanisms to sense and respond to changes in glucose levels. The efferent aspects of the central nervous system response to hypoglycemia are relatively well understood. In addition, it is accepted that the brain regulates food intake and energy balance. Obesity and diabetes both result from and cause alterations in the central nervous system function. Thus, it is reasonable to hypothesize that the brain also regulates daily glucose homeostasis and energy balance. However, little is known about how the brain actually senses and responds to changes in extracellular glucose. While there are neurons in the brain that change their action potential frequency in response to changes in extracellular glucose, most studies of these neurons have been performed using glucose levels that are outside the physiologic range of extracellular brain glucose. Thus, the physiologic relevance of these glucose-sensing neurons is uncertain. However, recent studies show that glucose-sensing neurons do respond to physiologic changes in extracellular glucose. This review will first investigate the data regarding physiologic glucose levels in the brain. The various subtypes of physiologically relevant glucose-sensing neurons will then be discussed. Based on the relative glucose sensitivity of these subtypes of glucose-sensing neurons, possible roles in the regulation of glucose homeostasis are hypothesized. Finally, the question of whether these neurons are only glucose sensors or whether they play a more integrated role in the regulation of energy balance will be considered.     

Haloarchaeal viruses: how diverse are they?

Hypersaline lakes are highly productive microbial environments that provide many advantages for microbial ecologists, including stable communities of relatively low diversity (mainly haloarchaea). An important component of these communities is comprised of their non-cellular parasites, i.e., their viruses. Few viruses of halobacteria (haloviruses) have been isolated and studied even though a wide selection of host species have been formally described (and easily cultured) for ten years. Hypersaline waters have been shown to contain very high concentrations of virus-like particles (at least 10(7) particles/ml), particularly fusiform particles, but laboratory isolations of new haloviruses have been very slow and the detailed study of selected examples even slower. Here we provide an outline of the reported haloviruses, including fusiform and unpublished isolates from this laboratory, and we discuss their diversity and the future directions for this research.     

Exercise and lactation: are they compatible?

Lactation is an energy-demanding physiological process for the maternal organism and life-giving for the offspring. Likewise, exercise is an energy-demanding process. This review addresses the compatibility of exercise during lactation. Human studies suggest no detrimental effect of exercise during lactation on milk composition and volume, infant growth and development, or maternal health. Studies also demonstrate improved cardiovascular fitness in lactating, exercising women and suggest a quicker return to pre-pregnancy body weight and a more positive sense of well-being, compared to sedentary controls. Findings from rodent studies, although of questionable value for humans, have generally shown no detrimental influence of exercise during pregnancy and lactation on pup growth and development. To date, findings suggest that exercise and lactation are compatible activities.