Heart rate increment analysis is not effective for sleep-disordered breathing screening in patients with chronic heart failure

Frequency domain analysis of heart rate variation has been suggested as an effective screening tool for sleep-disordered breathing (SDB) in the general population. The aim of this study was to assess this method in patients with chronic congestive heart failure (CHF). We included prospectively 84 patients with stable CHF, left ventricular ejection fraction (LVEF) <45% and sinus rhythm. The patients underwent polygraphy to measure the apnoea/hypopnoea index (AHI) and simultaneous Holter electrocardiogram monitoring to measure the power spectral density of the very low frequency component of the heart rate increment, expressed as the percentage of total power spectral density [% very low frequency increment (%VLFI)]. %VLFI could be determined in 54 patients (mean age, 52.8 ± 12.3 years; LVEF, 33.5 ± 9.8%). SDB defined as AHI ≥15 h⁻¹ was diagnosed in 57.4% of patients. Percent VLFI was not correlated with AHI ( r  =   0.12). Receiver-operating characteristic curves constructed using various AHI cut-offs (5–30 h⁻¹) failed to identify a %VLFI cut-off associated with SDB. The 2.4% VLFI cut-off recommended for the general population of patients with suspected SDB had low specificity (35%) and low positive and negative predictive values (35% and 54%, respectively). Heart rate increment analysis has several limitations in CHF patients and cannot be recommended as an SDB screening tool in the CHF population.     

Immunological IgE Cross-Reactions of Bovine and Human α-Lactalbumins in Cow's Milk Allergic Patients

Despite great homology with the equivalent human protein, bovine α-lactalbumin (B α-La), a major component of whey, has been identified as a major milk allergen. The aim of this study was to investigate the relationship between structure and IgE binding capacity in α-Las: (1) the importance of three-dimensional structure using native vs disulfide bridgereduced B α-La; and (2) the incidence of amino acid sequence divergence on specific IgE cross-reactivity to human vs bovine α-La. Purified native, reduced and S-carboxymethylated B α-La and human α-La (H alpha-LA) were prepared. Specific IgE of 20 sera from patients with clinically recognized cow's milk protein allergy and positive RAST tests to B α-La were measured in original direct and competitive ELISA inhibition tests. All sera containing specific anti-native B α-La IgE also reacted with denatured protein, but the IgE levels were generally lower, showing that three-dimensional structure is an important feature in B α-La allergenicity but that sequential epitopes are also exposed after protein denaturation. Despite lower IgE levels, all sera also gave significant IgE responses to H α-La. Competitive ELISA inhibition confirmed results obtained by direct ELISA. The demonstrated IgE cross-reactivity between B α-LA and H α-La could be related to the high degree of sequence homology between the two proteins but did not prove to have a clinical significance. However, it is of great interest for a study of the relationship between structure, IgE binding capacity and allergenicity in alpha-Las.     

Restless legs syndrome: Impact on sleep‐related breathing disorders

Restless legs syndrome (RLS) is a common chronic sensory‐motor neurological disorder that remains a clinical diagnosis. Most RLS patients present with sleep complaints in the form of initiation and/or maintenance insomnia as RLS has a circadian rhythmicity. An increased number of periodic leg movements during sleep (PLMS) is a supportive criterion in the diagnosis of RLS. Abnormalities in the central dopaminergic and iron systems are involved in the physiopathology of RLS. There is a higher prevalence of RLS and PLMS in sleep‐disordered breathing patients, particularly those with obstructive sleep apnoea (OSA), the most common sleep disorder in western societies. The complex mechanisms underlying the association between OSA, RLS and PLMS remain unclear. Untreated OSA can lead to adverse cardiovascular consequences due to cardio‐metabolic dysfunction. It remains controversial whether RLS could further adversely impact the cardiovascular consequences of OSA. The PLMS do not have an additive effect on the hypersomnia experienced by some sleep‐disordered breathing patients. Continuous positive airway pressure (CPAP) therapy is the most effective therapy for OSA. The presence of PLMS during CPAP treatment could be a marker of an incomplete resolution of sleep‐disordered breathing in the form of increased upper airway resistance syndrome, despite treatment. Dopaminergic agonists are the preferred agent for the treatment of RLS, and are indicated when RLS symptoms are frequent and affect quality of life. PLMS and RLS do not seem to contribute to the residual hypersomnia that can be observed in some sleep‐disordered breathing patients despite adequate compliance and effective CPAP therapy.     

Protective immunity in the rat model of congenital toxoplasmosis and the potential of excreted-secreted antigens as vaccine components

Toxoplasma infection is a major cause of severe foetal pathology both in humans and in domestic animals, particularly sheep. We have previously reported the development of an experimental model to study congenital toxoplasmosis in the rat. Here we demonstrate that, as in humans, total protection against congenital toxoplasmosis can be achieved regardless of the strain of Toxoplasma gondii used to infect rats, or when initial and challenge infections were carried out with different strains. Chronic infection is associated with a highly specific immunity that involves both B-and T-cell responses beginning at day 10 postinfection. The antibody isotype analysis revealed that whereas immunoglobulin (Ig)G2b is the major elicited isotype, no IgG1 antibodies are detected. T cell proliferation was assayed using crude Toxoplasma extracts or excretory-secretory antigens (ESA). The analysis of T cell supernatants showed the specific secretion of both interleukin-2 and interferon-gamma by activated T cells. Immunization of rats before pregnancy with either crude Toxoplasma extracts or with ESA elicited a B cell response that included antibodies of the IgG1 isotype and conferred on the newborns high levels of protection. Preliminary experiments of immunization using two HPLC-purified ESA, GRA2 and GRA5, conferred, a significant protection although to a lesser extent. This experimental model represents an attractive model for the identification of future vaccine candidates against congenital toxoplasmosis.     

Substance P activation of bronchoalveolar macrophages from asthmatic patients and normal subjects

The role of substance P in the pathogenesis of asthma is unclear. Animal studies suggest that it may be important, whereas human studies do not confirm this. Alveolar macrophages can be recovered easily by bronchoalveolar lavage (BAL) and stimulated in vitro. To assess the role of substance P in humans, we tested its ability to stimulate alveolar macrophages from six normal subjects and seven asthmatic patients. BAL cells were separated by adherence and alveolar macrophages constituted 95% of the adherent cell population. Four concentrations of substance P were used (10(-7), 10(-6), 10(-5), 10(-4) M). To assess the non-specific activation of alveolar macrophages we used three concentrations of lipopolysaccharides (LPS) (5, 10, 20 micrograms/ml). The stimulation of alveolar macrophages was assessed by the release of thromboxane B2 by radioimmunoassay. This study indicates that alveolar macrophages are stimulated by LPS but are poorly activated or not at all by substance P.     

SYNAPTIC MEMBRANE RESPONSES TO ACUTE AND CHRONIC ALCOHOL INTOXICATION IN HIGH ALCOHOL SENSITIVE (HAS) AND LOW ALCOHOL SENSITIVE (LAS) SELECTIVELY BRED RATS

HAS (high alcohol sensitive) and LAS (low alcohol sensitive)lines of rats have been selectively bred based on their differencesin ethanol-induced sleep time. In the present study, the twolines were compared to examine another central effect of acutealcohol intoxication: namely, hypothermia. As the disturbancesin membrane microorganization have been associated with thenervous system's sensitivity and tolerance to ethanol, the synapticplasma membrane fluidity and acute sensitivity to ethanol werealso evaluated by fluorescence polarization of DPH probes inthe HAS and LAS rats. The two lines did not differ in the magnitudeof their hypothermic response after acute injection of ethanol(3 g/kg body wt, i.p.). Although membranes in the HAS line wereslightly more rigid than in the LAS line, the level of membranedisordering after acute ethanol addition was identical for thetwo lines in the region examined with the DPH probe. Followingthe chronic intoxication of the rats, the two lines developedtolerance to the hypnotic and hypothermic effects of ethanol.In the same way, a membrane resistance (i.e. tolerance) to thedisordering effect of acute ethanol addition developed in theregion probed with DPH. In general, the LAS line showed a morepronounced level of tolerance than the HAS line at both thefunctional and membrane level. These results suggest that differentmeasures used to assess the depressant action of ethanol, suchas sleep time, hypothermia or membrane disordering, may notbe i and could indicate different genetic otigin also show thatseveral independent mechanisms besides simple adaptation tothe acute effects of ethanol may contribute to tolerance tothese effects.     

Scale development in zebrafish (Danio rerio)

In the course of an extensive comparative, structural and developmental study of the cranial and postcranial dermal skeleton (teeth and scales) in osteichthyan fishes, we have undertaken investigations on scale development in zebrafish (Danio (Brachydanio) rerio) using alizarin red staining, and light and transmission electron microscopy. The main goal was to know whether zebrafish scales can be used as a model for further research on the processes controlling the development of the dermal skeleton in general, especially epithelial–mesenchymal interactions. Growth series of laboratory bred specimens were used to study in detail: (1) the relationship of scale appearance with size and age; (2) the squamation pattern; and (3) the events taking place in the epidermis and in the dermis, before and during scale initiation and formation, with the aim of searching for morphological indications of epithelial-mesenchymal interactions. Scales form late in ontogeny, generally when zebrafish are more than 8.0 mm in standard length. Within a population of zebrafish of the same age scale appearance is related to standard length, but when comparing populations of different age the size of the fish at scale appearance is also related to age. Scales always appear first in the posterior region of the body and the squamation then extends anteriorly. Scales develop in the dermis but closely apposed to the epidermal–dermal boundary. Cellular modifications occurring in the basal layer of the epidermis and in the dermis before scale formation clearly indicate that the basal epidermal cells differentiate first, before any evidence of differentiation of the progenitors of the scale-forming cells in the dermis. This strongly suggests that scale differentiation could be initiated by the epidermal basal layer cells which probably produce a molecular signal towards the dermis below. Subsequently dermal cells accumulate close to the epidermis, and differentiate to form scale papillae. The late formation of the scales during ontogeny is due to a late colonisation of the dermis by the progenitors of the scale-forming cells. Because of their late formation during ontogeny and of their regular pattern of development, scales in zebrafish represent a good model for further investigations on the general mechanisms of epithelial-mesenchymal interactions during dermal skeleton development, and in particular for the study of the gene expression patterns.     

Exploring the reasons for non-participation of women in a breast cancer screening campaign

Study objectives: to determine the reasons for non-participationin a programme of screening for breast cancer. Design: semi-structuredtelephone interview. Setting: a pilot programme of screeningby mammography, targeted at all women aged between 50 and 70years in two regions of Switzerland. Population: a sample of33 non-participants were interviewed. Main results: few non-participantstook advantage of the screening tests for female cancers. However,only one-quarter were determined never to have a mammography.The others did not participate because of organizational problems(one-quarter) or because they did not understand what a mammographyinvolved (half). Conclusions: there is considerable scope forincreasing the rate of participation. Efforts must be made toimprove the information directed at the socially less favoured(the objectives of the screening and the organizational arrangements).Family doctors are frequently consulted and are best placedto communicate this information. They should be encouraged toplay a much more active part in this respect.     

Epstein-Barr virus in familial Hodgkin's disease

Summary Hodgkin's disease (HD) has been found to be linked to Epstein-Barr virus (EBV). Familial HD (FHD) may be related to a possible unknown agent. We have determined whether EBV small RNAs (EBERs) were found in Reed-Sternberg cells from FHD. Five families were studied for histological subtype and EBER presence. There was a striking similarity in FHD subtypes of each family and 3/11 (27%) of the cases were EBER positive. In conclusion, EBV EBERs are only infrequently found in FHD and other factors including viruses different from EBV should be further investigated in FHD.