Farm-derived Gram-positive bacterium Staphylococcus sciuri W620 prevents asthma phenotype in HDM- and OVA-exposed mice.

BACKGROUND: Farm-derived dust samples have been screened for bacteria with potential allergo-protective properties. Among those was Staphylococcus sciuri W620 (S. sciuri W620), which we tested with regard to its protective capacities in murine models of allergic airway inflammation. METHODS: We employed two protocols of acute airway inflammation in mice administering either ovalbumin (OVA) or house dust mite extract (HDM) for sensitization. Mechanistic studies on the activation of innate immune responses to S. sciuri W620 were carried out using human primary monocytic dendritic cells (moDC) and co-culture with autologous T cells. RESULTS: The allergo-protective properties of S. sciuri W620 were proven in a T(H)2-driven OVA model as well as in a mixed T(H)1/T(H)2 phenotype HDM model as demonstrated by abrogation of eosinophils and neutrophils in the airways after intranasal treatment. In the HDM model, lymph node cell T(H)1/T(H)2 signature cytokines were decreased in parallel. Studies on human moDC revealed an activation of TLR2 and NOD2 receptors and initiation of DC maturation following incubation with S. sciuri W620. Cytokine expression analyses after exposure to S. sciuri W620 showed a lack of IL-12 production in moDC due to missing transcription of the IL-12p35 mRNA. However, such DC selectively supported T(H)1 cytokine release by co-cultured T cells. CONCLUSION AND CLINICAL RELEVANCE: Our proof-of-concept experiments verify the screening system of farm-derived dust samples as suitable to elucidate new candidates for allergo-protection. S. sciuri W620 was shown to possess preventive properties on airway inflammation providing the basis for further mechanistic studies and potential clinical implication.

Development and genetic influence of the rectal bacterial flora of newborn calves.

The aim of the study was to investigate a dynamic change in the rectal flora of calves as well as to study a genetic influence on the intestinal microflora of calves. The bacterial community of fecal samples from calves was examined by PCR single strand conformation polymorphism (PCR-SSCP) in two independent studies. In study one 14 newborn calves of the same farm were examined. Sampling was conducted directly after delivery (meconium) and after 6 h, 12 h, 24 h, 48 h, 3 d, 7 d, 14 d and 42 d of life. In study two 6 twin calves and their coresident of the same age and farm were analysed in order to study for the first time whether genetic predisposition of the host may influence the fecal microflora. All calves were weaned directly after delivery and received pumped colostrum without direct contact to other farm animals. After delivery and during the first 12h of life the SSCP profiles were simple, but became more complex since the bacterial diversity increased with time in all calves. It became obvious that the intra-individual band-pattern similarity decreased over time and inter-individual similarity was low. The analysis of fecal samples from twin calves revealed higher similarity in SSCP profiles for twins compared to their coresident indicating that the individual microflora might be genetically or epigenetically influenced. The insight that there are several conformities between intestinal microfloras of healthy calves and that there might be genetic influence on the fecal flora could help to prevent diarrhoeal diseases in the future.

Impact of an early weighing policy on neonatal hypernatraemic dehydration and breast feeding.

AIMS: To ascertain the effect of a policy of early weighing on the detection and severity of neonatal hypernatraemic dehydration (NHD) and on breastfeeding rates in the short and medium term. METHODS: A policy of weighing infants at 72-96 h was introduced from 1 July 2004. Two time periods were studied: pre-policy and post-policy (18 months each). Babies <28 days of age referred to hospital from the community who, on investigation, had plasma sodium concentrations of >145 mmol/l were identified. Age, plasma sodium concentration, percentage loss of body weight at presentation, breastfeeding rates at discharge and at 8 weeks, and complications due to hypernatraemia or its management were compared between the two groups. RESULTS: 60 cases of NHD were identified: 23 before and 37 after introduction of the policy. After the policy, there was earlier recognition of NHD (median 3 vs 6 days), lower percentage weight loss (11% vs 15%), smaller increase in sodium (147 vs 150 mmol/l), and higher breastfeeding rate at discharge (73% vs 22%) and 8 weeks (57% vs 22%). All the differences were significant (p<0.01). There was one death in the pre-policy group, and none in the post-policy group. CONCLUSIONS: Weighing babies early coupled with appropriate lactation support resulted in the early recognition of NHD, with less dehydration, less severe hypernatraemia, and higher breastfeeding rates in the short and medium term.

Time domain correlation analysis of heart rate variability in preterm neonates.

BACKGROUND AND AIM: A fuller understanding of the neural control mechanisms of heart rate during the early stages of human development would be of great value to obstetric and neonatal management. In this paper, we investigate the correlation between heart rate variability (HRV) and other physiological parameters such as blood pressure and respiration in preterm neonates with the aim of developing a numerical model to explain and predict heart rate variability. STUDY DESIGN AND SUBJECTS: All the required data are readily available for premature babies who are routinely monitored while being nursed in intensive care, and we have collected large data sets for a random group of such neonates. For the quantitative analysis of the data, we have developed a time domain correlation method, which has a number of advantages over the more commonly used power spectral analysis. We have been able to study the dynamics of the different frequency components of HRV by this method. RESULTS: Highly correlated behaviour of the different HRV components, previously observed in our work on fetal HRV, is also present in the neonate, with similar characteristic time constants. Furthermore, the correlation of high-frequency (HF) oscillations of HRV with respiration and that of low-frequency (LF) oscillations of HRV with blood pressure are demonstrated on timescales of a single oscillation. In neonates receiving artificial ventilation, the correlation between HRV and respiration depends on the type of ventilation involved and assumes opposite polarities for the two main types of equipment currently in use. CONCLUSION: We demonstrate that it is possible to analyse HRV quantitatively by calculating the relative gains and characteristic time constants for the correlated parameters and components.

Determination of red cell volume in infants needing blood transfusion.

The total circulating red cell volume (RCV) is a better guide to the oxygen-carrying capacity of the blood in the whole circulation than is the haemoglobin concentration (Hb) or haematocrit in a blood sample. Pre- and post-transfusion RCV (and blood volume (BV)) may be determined by flow cytometry by exploiting antigen differences between transfused donor red cells and the recipient's red cells. This paper describes the use of red cell antigen differences of Duffy, Kidd, MN and RhD between donor and recipient. In 20 infants, transfused on 21 occasions, pretransfusion RCV ranged from 12 to 39 mL kg(-1) body weight. Only at one transfusion could no usable donor-recipient antigen differences be exploited. Measurement of RCV, used routinely, may determine the transfusion requirements of sick infants more accurately, with the aim of normalizing RCV and BV--securing euvolaemia--at the end of the transfusion. This may allow a complete correction of the RCV deficiency at the first occasion of transfusion. This approach may reduce donor exposures and also optimize oxygen transport and organ perfusion of the infant undergoing intensive management, perhaps leading ultimately to improved survival rates and fewer long-term complications of neonatal intensive care.

Pharmacodynamic interaction between mibefradil and other calcium channel blockers.

Briefly after withdrawal of the (T-type) calcium channel blocker mibefradil from the market, four cases of life-threatening interaction of mibefradil with dihydropyridines were reported. We investigated in vitro whether mibefradil interacts with a dihydropyridine, as described for other non-dihydropyridine compounds. Rat working hearts were used to examine functional interactions between amlodipine and mibefradil. Gallopamil and another T-type-channel blocker, ethosuximide, were included for comparison. Effects of mibefradil, (+)- and (-)-gallopamil on [3H](+)-isradipine binding were studied in membranes from tsA201-cells transfected with alpha(1c)-, alpha(2)delta-, and beta(1a)- or beta(2a)-calcium channel subunits. Mibefradil increased negative inotropic effect of amlodipine, but not of gallopamil. Gallopamil and ethosuximide showed no influence on contractile effects of amlodipine. Furthermore, mibefradil concentration-dependently caused bradycardic rhythm disturbance. The same type of arrhythmia was observed combining low concentrations of mibefradil with amlodipine, or with gallopamil, respectively. Amlodipine alone, or the combination of gallopamil or ethosuximide with amlodipine did not cause any arrhythmia. Binding studies showed a concentration-dependent positive allosteric interaction between [3H](+)-isradipine and mibefradil, but not with [3H](+)-isradipine and gallopamil enantiomers. Molecular and functional evidence points to an interaction between a dihydropyridine and mibefradil. Mibefradil caused rhythm disturbances and potentiation of negative inotropy when combined with amlodipine.

Confidential enquiry into deaths due to prematurity.

The aim of this study was to audit the management of neonatal respiratory distress syndrome (RDS) in a geographically defined population using a retrospective peer review of case notes. The subjects were 49 infants of 24-36 wk gestation with a birthweight >499 g, and dying as a consequence of prematurity at <1 y of age in Wales during 1996. Forty-four infants (90%) were delivered in a unit with staff experienced in the management of preterm birth. Of the 30 infants <30 weeks' gestation, 29 (97%) received neonatal intensive care on a (sub)regional unit. Predelivery corticosteroids were indicated in 34 cases and administered in 31 (91%). Resuscitation at birth was indicated in 47 infants and conducted satisfactorily in 42 (89%). Temperature on admission to the neonatal unit was not recorded in 7 infants; in the other 42 it was >35.5 degrees C in 21 (50%). Early surfactant therapy was administered to 31/34 (91%) infants still intubated 120 min after birth, but was given within 30 min to only 8 (24%). Mechanical ventilation was assessed in 41 infants and considered to be good in 23 (56%). Cardiovascular therapy was evaluated in 40 infants requiring active support and considered to be good in 31 (78%). We concluded that neonatal RDS was generally well managed, thermal care during resuscitation was poor, surfactant should be administered more promptly, and deficiencies in the management of ventilation were common and related mainly to poor anticipation and a slow response to problems.

Body size and subcutaneous fat patterning in adolescence.

Factors that influence low birth weight at term may also be associated with subcutaneous fat patterning in later life. This hypothesis was investigated in a comparative (retrospective) cohort study. The subjects, born in Cardiff between 1975 and 1977, were of mean age 15.7 years. Cases (low birth weight (< 2500 g) at term) were matched with controls (normal birth weight (3000-3800 g) at term) for sex, parity, place of birth, date of birth, and gestation. Subscapular skinfold (an index of central subcutaneous fat) and triceps skinfold (an index of peripheral subcutaneous fat) were measured using a Holtain skinfold caliper. The differences (cases minus controls) (95% confidence interval) for subscapular and triceps skinfolds were respectively -0.3 mm (-1.74 to 1.14) and -0.48 mm (-1.75 to 0.79). These findings are inconsistent with the hypothesis that low birth weight at term is associated with subcutaneous fat patterning in adolescence.

Birth weight at term and lung function in adolescence: no evidence for a programmed effect.

It has been suggested that factors which influence low birth weight at term may be associated with reduced lung function in later life. This hypothesis was investigated in a comparative (retrospective) cohort study of 164 matched pairs of subjects where the observers responsible for tracing and studying the subjects were unaware of their case or control status. The subjects, born in Cardiff between 1975 and 1977, were of mean age 15.7 years. Cases (low birth weight (< 2500 g) at term) were matched with controls (normal birth weight (3000-3800 g) at term) for sex, parity, place of birth, date of birth, and gestation. Lung function was measured using a portable spirometer. The corrected mean differences (95% confidence interval) in forced vital capacity (FVC) and flow when 50% or 25% of the FVC remains in the lungs between the cases and controls were respectively -41 ml (-140 to 58), -82 ml/sec (-286 to 122), and -83 ml/sec (-250 to 83). None of these differences were statistically significant. These results are inconsistent with the hypothesis that low birth weight at term is associated with reduced lung function in adolescence.

Convulsive status epilepticus in children treated for epilepsy: an assessment of management.

The acute care and further management plans accorded to eight children, all already on treatment for epilepsy, admitted to hospital with a total of 17 episodes of convulsive status epilepticus were examined. Emergency treatment was appropriate, but longer-term management tended to be less than adequate. The causes of status epilepticus were not considered before discharge on 10 occasions. Advice on simple preventative measures was rarely given to the parents. Junior staff require further training in these areas.

Relation between birth weight at term and systolic blood pressure in adolescence.

OBJECTIVE: To examine whether birth weight is related to systolic blood pressure during adolescence. DESIGN: Retrospective (comparative) cohort study. The observers who traced and studied the subjects were unaware of their case-control status. SUBJECTS: 330 subjects were born in Cardiff in 1975-7. Cases who were low birth weight at term (< 2500 g) were matched with controls of normal birth weight (3000-3800 g) at term. MAIN OUTCOME MEASURES: Systolic blood pressure measured by random zero sphygmomanometry in the subject's right arm with the subject supine, corrected for size and age. RESULTS: The mean age at examination was 15.7 years. The mean systolic blood pressure of the cases was 105.8 mm Hg and of the controls 107.5 mm Hg. The corrected difference (95% confidence interval) in systolic blood pressure between the cases and controls was 1 mm Hg (-3 to +1 mm Hg; two tailed probability 0.33). CONCLUSION: Systolic blood pressure in adolescents of low birth weight is not significantly different from that of adolescents of normal birth weights.

Prevalence of incidental intraspinal lipoma of the lumbosacral spine as determined by MRI.

STUDY DESIGN: The prevalence and appearance on MRI of lipomas of the filum terminale was studied in a random population referred to MRI for evaluation of the lumbosacral spine. The MRI scans of 100 patients selected at random were retrospectively reviewed. OBJECTIVES: The study sought to determine the frequency and MRI appearance of incidental filum lipomas in a random population. SUMMARY OF BACKGROUND DATA: Postmortem studies have reported a 4%-6% incidence of occult fibrolipomas of the filum terminale in what were thought to be otherwise normal spinal cords. The improved resolution of MRI imaging allows the detection of small amounts of fat associated with the filum terminale that heretofore had not been demonstrated on radiologic imaging examinations. METHODS: The lumbosacral spine unenhanced MRI scans of 100 patients not previously operated upon were selected at random and were retrospectively reviewed by two of the authors (EB and JCM). RESULTS: Of the 100 MRI examinations reviewed, four patients were found to have small lipomas of the filum terminale. No spinal dysraphism or cord tethering were present in these four patients. Their clinical symptoms were related to disc herniation in two patients, spinal stenosis in one, and discitis in one. The lipomatous tissue was hyperintense to cerebrospinal fluid (CSF) on T1-weighted images and hypointense to CSF on T2-weighted images. CONCLUSIONS: Incidental lipomas of the filum terminale were present in 4% of 100 lumbosacral spine MRI examinations in a random population.

The induction of ovulation with pulsatile gonadotrophin-releasing hormone (GnRH) administration in hyperandrogenic women after down-regulation with buserelin or suppression with an oral contraceptive.

The hypothalamic-pituitary axis of 22 hyperandrogenic infertile women had suppression with either the gonadotrophin-releasing hormone (GnRH)-analogue buserelin (n = 12) or with an oestrogen-gestagen compound (Diane; n = 12). This was followed by pulsatile GnRH application for inducing ovulation (Zyklomat). In terms of ovulation and pregnancy rates the buserelin pre-treatment was more effective than the steroid pre-treatment, especially in hyperandrogenic non-polycystic ovaries (PCO).

MR imaging of "spray heads": toluene abuse via aerosol paint inhalation.

PURPOSE: Three male patients with a history of spray-paint inhalation are presented. METHODS: Spin-echo MR was used to evaluate the central nervous system changes secondary to toluene inhalation delivered via spray-paint fumes. RESULTS: The remarkable findings included the loss of cerebral and cerebellar gray-white matter discrimination, scattered multifocal deep white matter lesions, and gross generalized atrophy of the cerebrum, the cerebellum, and the corpus callosum. CONCLUSION: Although the observed changes are nonspecific, combined with a positive history the diagnosis of inhalation toluene abuse can be made on the basis of consistent MR findings.