Selective localisation of neuro-specific T lymphocytes in the central nervous system

Using experimental autoimmune encephalomyelitis (EAE) in the rat as a model of central nervous system (CNS) inflammation, activated and quiescent T lymphocytes with different antigen specificities were labelled with the fluorescent dye Hoechst 33342 and tested by fluorescence microscopy for their ability to accumulate in different regions of the spinal cord and in other organs at varying times post inoculation. With this highly sensitive assay it was found that activated myelin basic protein (MBP)-specific T cell lines accumulated in the spinal cord (a 1000-fold increase in the lumbar/sacral region by day 4) and caused clinical signs of EAE. In contrast, interleukin-2 (IL-2)-maintained (quiescent) MBP-specific T cell lines failed to accumulate in the CNS and cause disease. Activated ovalbumin (OA)-specific and purified protein derivative of tuberculin (PPD)-specific T cell lines were also found at significantly higher levels in the spinal cord than non-activated cells although they failed to accumulate to a substantial degree when injected alone. When injected with activated MBP-specific T cells the activated OA- and PPD-specific cell lines accumulated in the spinal cord following initial accumulation of the MBP-specific cells, demonstrating that during the inflammatory process there is considerable non-specific recruitment of cells into the inflammatory site. CNS accumulation of activated MBP-specific T cell lines occurred 1-2 days later in irradiated animals than in non-irradiated recipients. This was consistent with irradiated animals also exhibiting a later onset of disease and suggests that irradiation may directly affect the endothelium in a way that makes it less adhesive. In conclusion, this study demonstrates that activated lymphocytes of any specificity enter the spinal cord, and that the neuro-antigen specific cells accumulate there and lead to the recruitment of other cells. Non-activated cells, even those with neural antigen specificity fail to enter the cord. Understanding the nature of what an 'activated' lymphocyte is may allow us to design strategies to inhibit such immune-mediated inflammation.     

Improving recovery following cardiac surgery: a randomized clinical trial*

To enhance individual and family health during recovery from heart surgery, this study employed nursing interventions based on self-efficacy and family stress theory during the hospitalization period and for 3 months thereafter. The effectiveness of the interventions were assessed through a randomized trial in which 67 prospective bypass and valve surgery patients, aged 30-77 years, and their spouses, were allocated either the experimental interventions or usual care and followed for 6 months. At 3 months post-surgery, the only statistically significant differences between the experimentals and controls were on perceived self-efficacy for lifting and tolerating emotional distress. At 6 months no significant differences were found on individual or family measures. Analyses revealed that age, gender and preoperative cardiac status significantly affected individual recovery. The study is continuing with a larger sample in order to explicate the recovery process and to better determine whether a low intensity nursing intervention can effect changes in individual and family recovery.     

HEMATOCRIT VALUES DURING PREGNANCY IN A NURSE-MIDWIFERY CASELOAD

This article reviews the normal hematologic changes in pregnancy and the kinetics of iron metabolism. The differences between iron depletion and anemia are described. The hematocrit levels of a nurse-midwifery caseload in a tertiary-care setting are described and compared with recently published population norms. Hematocrits of the sample compared favorably to the population hematocrits until 24 weeks' gestation, when the sample hematocrit mean became statistically lower and remained that way throughout pregnancy. Further analysis was done on the sample hematocrits, comparing differences in parity, age, pregnancy spacing, and AS versus AA hemoglobin. Parous women with a pregnancy interval >12 months had a higher mean hematocrit then nulliparous women. Mean hematocrits of age groups varied significantly only at the 29–32-week interval, with women younger than 18 having lower mean hematocrits than those ≥18. A trend of women with AS hemoglobin having higher hematocrits than women with AA hemoglobin was identified, reaching statistical significance at the 29–32-week interval.     

In vivo MRI of cancer cell fate at the single-cell level in a mouse model of breast cancer metastasis to the brain.

Metastasis (the spread of cancer from a primary tumor to secondary organs) is responsible for most cancer deaths. The ability to follow the fate of a population of tumor cells over time in an experimental animal would provide a powerful new way to monitor the metastatic process. Here we describe a magnetic resonance imaging (MRI) technique that permits the tracking of breast cancer cells in a mouse model of brain metastasis at the single-cell level. Cancer cells that were injected into the left ventricle of the mouse heart and then delivered to the brain were detectable on MR images. This allowed the visualization of the initial delivery and distribution of cells, as well as the growth of tumors from a subset of these cells within the whole intact brain volume. The ability to follow the metastatic process from the single-cell stage through metastatic growth, and to quantify and monitor the presence of solitary undivided cells will facilitate progress in understanding the mechanisms of brain metastasis and tumor dormancy, and the development of therapeutics to treat this disease.     

Identification of a parathyroid hormone in the fish Fugu rubripes.

A PTH gene has been isolated from the fish Fugu rubripes. The encoded protein of 80 amino acid has the lowest homology with any of the PTH family members. Fugu PTH(1-34) had 5-fold lower potency than human PTH(1-34) in a mammalian cell system. INTRODUCTION: Parathyroid hormone (PTH) is the major hypercalcemic hormone in higher vertebrates. Fish lack parathyroid glands, but there have numerous attempts to identify and isolate PTH from fish. MATERIALS AND METHODS: Polymerase chain reaction (PCR) was performed with primers based on preliminary data from the Joint Genome Institute database. PCR amplification was performed on genomic DNA isolated from Fugu rubripes. PCR products were purified and DNA was sequenced. All sequence was confirmed from more than one independently amplified PCR product. Multiple sequence alignments were carried out, and the percentage of identities and similarities were calculated. An unrooted phylogenetic tree, using all the known PTH and PTH-related protein (PTHrP) amino acid sequences, was determined. Synthetic peptides were tested in a biological assay that measured cyclic adenosine 3',5'-monophosphate formation in UMR106.1 cells. Rabbit polyclonal antisera specific for N-terminal human PTHrP and one rabbit polyclonal antiserum specific for N terminus hPTH were used to test the cross-reactivity with fPTH(1-34) in immunoblots.     

The Association of Different Measures of Insulinaemia with Vascular Risk Factors in Healthy Normoglycaemic Normotensive Non-obese Men and Women

Hyperinsulinaemia is said to be a risk factor for cardiovasculardisease, but the extent to which different insulinaemic measuresare associated with vascular risk factors in ostensibly healthyindividuals, and whether they operate independently in men andwomen, remains uncertain. The association between risk factors and various insulinaemicmeasures was examined in 148 men and 118 women who were normoglycaemic,normotensive, and non-obese (body mass index in men <27,in women <25). A 75 g glucose tolerance test was administeredafter blood sampling for fibrinogen, lipids, lipoproteins andinsulin. Insulin was also measured after 1 and 2 hours. Significantunivariate correlations (p<0.01) were most consistently recordedbetween insulinaemic measures and fasting serum triglyceridesin men and women, whilst systolic blood pressure only correlatedwith insulinaemia in women, and diastolic blood pressure correlatedwith fasting and 2 hour insulinaemic measures in men and women.Inconsistent associations were noted with total serum cholesterolin men and women, with high density lipoprotein cholesterol,body mass index, apoprotein B and A1 in men, and with fibrinogenin women. Age was not correlated with any insulinaemic measurein men or women. Differences in vascular risk factors between quintiles of theinsulinaemic measures were examined, after correction for bodymass index. The dominant association with fasting and post-glucoseload insulinaemic measures was with triglycerides, especiallyin women, with less frequent graded differences between quintilesobserved for total cholesterol, and diastolic and systolic bloodpressures in men and women. The incidence of other risk factors often only differed in thelowest or highest quintile in comparison to other quintiles,suggesting a threshold rather than a graded effect. Furthermore,differences in HDL cholesterol and apoprotein B were only recordedfor top quintiles of post-glucose challenge/integrated insulinaemicmeasures in men, whilst serum fibrinogen concentrations onlydiffered significantly in women in the top insulinaemic areaunder the curve quintile. In the absence of additional risk factors such as diabetes,hypertension and obesity, insulinaemic measures are not consistentlyrelated to blood pressure and measures of lipid metabolism andcoagulation, and are thus a weak predictor of other cardiovascularrisk factors. The vascular risk profile associated with insulinappears somewhat different in apparently healthy men and women.     

General practitioners: child accident prevention and 'The Health of the Nation'

It has recently been suggested in the ‘Health of the Nation’that specific accident prevention activities should be undertakenby general practitioners. This study reports the findings froma survey of general practitioners in Nottinghamshire assessingknowledge, attitudes and current practices in accident prevention.The findings suggest that more than two-thirds of respondinggeneral practitioners are aware of the extent of childhood mortalityfrom accidental injuries and of the risk factors for accidentalinjury. Knowledge scores were higher for women, those aged 44years and under, those on the child health surveillance list,those with experience of hospital or community paediatrics,and those with postgraduate qualifications in paediatrics. Morethan 50% of general practitioners hold positive views towardsthe activities suggested in the ‘Health of the Nation’and more than 40% are already carrying out such activities.Positive attitudes are more commonly held in women and thoseon the child health surveillance list. There was a significantcorrelation between knowledge score and attitude score. Forall accident prevention activities covered in the questionnaire,fewer practitioners undertook an activity than held a positiveattitude towards that activity. Accident prevention work iscurrently more likely to be undertaken by general practitionerson an opportunistic basis than on a systematic population basis.If general practitioner intervention is demonstrated to be effective,a shift towards a population approach may be more successfulin reducing injury rates.     

Randomized Controlled Trial of Hands‐and‐Knees Positioning for Occipitoposterior Position in Labor

ABSTRACT: Background: Hands‐and‐knees positioning during labor has been recommended on the theory that gravity and buoyancy may promote fetal head rotation to the anterior position and reduce persistent back pain. A Cochrane review found insufficient evidence to support the effectiveness of this intervention during labor. The purpose of this study was to evaluate the effect of maternal hands‐and‐knees positioning on fetal head rotation from occipitoposterior to occipitoanterior position, persistent back pain, and other perinatal outcomes. Methods: Thirteen labor units in university‐affiliated hospitals participated in this multicenter randomized, controlled trial. Study participants were 147 women laboring with a fetus at ≥37 weeks’ gestation and confirmed by ultrasound to be in occipitoposterior position. Seventy women were randomized to the intervention group (hands‐and‐knees positioning for at least 30 minutes over a 1‐hour period during labor) and 77 to the control group (no hands‐and‐knees positioning). The primary outcome was occipitoanterior position determined by ultrasound following the 1‐hour study period and the secondary outcome was persistent back pain. Other outcomes included operative delivery, fetal head position at delivery, perineal trauma, Apgar scores, length of labor, and women's views with respect to positioning. Results: Women randomized to the intervention group had significant reductions in persistent back pain. Eleven women (16%) allocated to use hands‐and‐knees positioning had fetal heads in occipitoanterior position following the 1‐hour study period compared with 5 (7%) in the control group (relative risk 2.4; 95% CI 0.88–6.62; number needed to treat 11). Trends toward benefit for the intervention group were seen for several other outcomes, including operative delivery, fetal head position at delivery, 1‐minute Apgar scores, and time to delivery. Conclusions: Maternal hands‐and‐knees positioning during labor with a fetus in occipitoposterior position reduces persistent back pain and is acceptable to laboring women. Given this evidence, hands‐and‐knees positioning should be offered to women laboring with a fetus in occipitoposterior position in the first stage of labor to reduce persistent back pain. Although this study demonstrates trends toward improved birth outcomes, further trials are needed to determine if hands‐and‐knees positioning promotes fetal head rotation to occipitoanterior and reduces operative delivery. (BIRTH 32:4 December 2005)