The relation between pre-eclampsia at term and neonatal encephalopathy

OBJECTIVES: To determine whether pre-eclampsia, hypothesised to be an inflammatory condition, is associated with fever in term labour, and confirm and examine the reported association of pre-eclampsia at term with neonatal encephalopathy. DESIGN: Prospective cohort study. SETTING: A Dublin teaching hospital. PARTICIPANTS: 6163 women in labour with singleton pregnancies at term at low risk for intrapartum hypoxia, recruited to a randomised trial examining the effect of admission cardiotocography on neonatal outcome. RESULTS: Pre-eclampsia was associated with maternal fever > 37.5 degrees in labour (odds ratio (OR) 3.39, 95% confidence interval (CI) 2.1 to 5.4); this was independent of obstetric intervention (adjusted OR 2.07, 95% CI 1.24 to 3.47). Pre-eclampsia was associated with neonatal encephalopathy (OR 25.5, 95% CI 8.4 to 74.7); this too was independent of obstetric intervention (adjusted OR 18.5, 95% CI 5.9 to 58.1). Cord arterial pH values were significantly lower in pre-eclamptics (7.20 v 7.24), although severe cord acidaemia was not significantly more common (OR 2.91, 95% CI 0.7 to 9.9). The association of pre-eclampsia with encephalopathy was independent of maternal fever (adjusted OR 16.5, 95% CI 5.1 to 54) and cord acidaemia (adjusted OR 13.5, 95% CI 3.2 to 56.7). CONCLUSIONS: The association of pre-eclampsia with maternal fever at term supports the hypothesis that pre-eclampsia is an inflammatory condition. The association of pre-eclampsia with neonatal encephalopathy is independent of obstetric intervention and cannot be explained by either acidaemia or maternal fever. A systemic inflammatory response in the fetus, perhaps secondary to oxidative stress, could explain the link between maternal pre-eclampsia and neonatal encephalopathy, and this may occur through cerebral vasoconstriction.     

The cellular responses of articular cartilage to sharp and blunt trauma

OBJECTIVE: To determine the response of immature articular cartilage to both sharp and blunt trauma in terms of cell death, cell proliferation and matrix synthesis. DESIGN: Blunt wounds were made with a trephine in full depth immature bovine articular cartilage explants which were cut in half through the center of the trephine wound with a sharp scalpel to produce blunt and sharp trauma on the same explant. Explants were maintained in culture for up to 10 days. Prior to fixation at days 2, 5 and 10, medium was supplemented with 10 microCi ml-1 35S-sulphate, [3H]-proline or [3H]-thymidine for 24h to assess matrix synthesis and cell proliferation. Cell death was assessed using a Live/Dead label. RESULTS: In the case of blunt wounds, a band of cell death was observed adjacent to the lesion edge. Microautoradiography demonstrated little radiolabel incorporation and, therefore, no new matrix synthesis or cell proliferation within this region. In contrast, wounds made with a sharp scalpel showed restricted cell death, with radiolabel incorporation adjacent to the lesion edge at all time points. This demonstrated not only chondrocyte proliferation and new matrix synthesis at the wound margin, but also an up-regulation of matrix synthesis adjacent to the lesion edge. CONCLUSIONS: In terms of clinical relevance, the use of sharp precise instruments during the surgical management of cartilage defects may be necessary to reduce cell death and promote matrix elaboration at the lesion edge in order to facilitate successful integration.     

Cost-effectiveness of an intensive group training protocol compared to physiotherapy guideline care for sub-acute and chronic low back pain: design of a randomised controlled trial with an economic evaluation. [ISRCTN45641649]

Background

Low back pain is a common disorder in western industrialised countries and the type of treatments for low back pain vary considerably.

Methods

In a randomised controlled trial the cost-effectiveness and cost-utility of an intensive group training protocol versus physiotherapy guideline care for sub-acute and chronic low back pain patients is evaluated. Patients with back pain for longer than 6 weeks who are referred to physiotherapy care by their general practitioner or medical specialist are included in the study. The intensive group training protocol combines exercise therapy with principles of behavioural therapy ("graded activity") and back school. This training protocol is compared to physiotherapy care according to the recently published Low Back Pain Guidelines of the Royal Dutch College for Physiotherapy. Primary outcome measures are general improvement, pain intensity, functional status, work absenteeism and quality of life. The direct and indirect costs will be assessed using cost diaries. Patients will complete questionnaires at baseline and 6, 13, 26 and 52 weeks after randomisation.

Discussion

No trials are yet available that have evaluated the effect of an intensive group training protocol including behavioural principles and back school in a primary physiotherapy care setting and no data on cost-effectiveness and cost-utility are available.

     

Preeclampsia and the systemic inflammatory response

Normal pregnancy is associated with a systemic inflammatory response. The response is exacerbated in preeclampsia and can account for its clinical features. Many of the physiologic changes of normal pregnancy are part of an acute-phase reaction, which is generated by an inflammatory response. The placenta is the proximal cause of these problems. There are several possible placental factors that may evoke the inflammatory responses that currently are being investigated. The special susceptibility of obese women, or those with diabetes or chronic hypertension, to preeclampsia is explained by the chronic systemic inflammatory responses that these women have. The clinical implications of these concepts are discussed.     

Point mutations causing the McLeod phenotype

BACKGROUND: The McLeod phenotype is defined by absence of Kx, weakening of Kell system antigens, and acanthocytosis. Individuals with the McLeod phenotype usually develop late-onset neuromuscular abnormalities. Gene deletions, insertions, and point mutations that affect RNA splicing or that lead to premature stop codons have been reported to cause the McLeod phenotype. The McLeod phenotype may also be caused by mutations at a different splice site and by a novel mutation encoding an amino acid substitution that prevents transport to the cell surface. STUDY DESIGN AND METHODS: The coding and flanking intron regions of XK from four male, unrelated individuals with the McLeod phenotype and non-chronic granulomatous disease were sequenced and compared with the wild type sequence. Genomic DNA was amplified by PCR, and the products were sequenced. In one case, the mutant cDNA was expressed in a heterologous cell, and cell surface expression was determined. RESULTS: Three individuals with the McLeod phenotype had mutations that disrupted conserved GT sequences present at RNA splice sites. Two of them had G>C mutations at the 5' splice site of intron 1, and one had a G>A mutation at the 5' splice site of intron 2. One person with the McLeod phenotype had a 746C>G mutation in exon 3 encoding an R222G substitution. In a transfected cell, the expressed protein from the latter mutant did not travel to the cell surface. CONCLUSION: The McLeod phenotype may be caused by several different mutations.     

Different calcium sources are narrowly tuned to the induction of different forms of LTP

The essential role of calcium in the induction of long-term potentiation (LTP) has been well established. In particular, calcium influx via the N-methyl-D-aspartate (NMDA) receptor (NMDAR) is important for LTP induction in many pathways. However, the specific roles of other calcium sources in hippocampal LTP are less clear. The aim of the present study was to determine the appropriate conditions and extent to which non-NMDAR Ca(2+) sources contribute to the induction of different forms of LTP in area CA1 of hippocampal slices. Increasing numbers of theta-burst trains (1, 4, and 8 TBS) induced LTP of increasing magnitude and persistence. Inhibition of ryanodine receptors caused inhibition of weak LTP induced by 1 TBS, but had no effect on more robust forms of LTP. Inhibition of IP3 receptors inhibited moderate LTP induced by 4 TBS, but had no effect when 1 TBS or 8 TBS were used. Inhibition of L-type voltage-dependent Ca(2+) channels inhibited strong LTP induced by 8 TBS, but had no effect on weaker forms of LTP. These results show that different Ca(2+) sources have different thresholds for activation by TBS trains. Furthermore, each Ca(2+) source appears to be tuned to the induction of a different form of LTP. Such tuning could reflect an important link between different LTP induction and maintenance mechanisms.     

Implications of cytochrome P450 2C9 polymorphism on warfarin metabolism and dosing

Warfarin is an anticoagulant available as a racemic mixture. The R- and S-isomers differ with respect to relative plasma concentrations, clearance, potency, sites of metabolism, and cytochrome P450 (CYP) isoenzymes responsible for metabolism. S-Warfarin, the more potent isomer, is metabolized primarily by CYP2C9. Genetic polymorphisms resulting from single amino acid substitutions reduce the metabolic capability of 2C9. A reduction in warfarin metabolism due to genetic polymorphism may explain the increased warfarin response and bleeding episodes in some patients. Clinical studies showed an increased plasma level of S-warfarin, decreased clearance of S-warfarin, increased frequency of bleeding, and prolongation of hospitalization in patients with variant CYP2C9 alleles. Adverse outcomes associated with warfarin possibly could be avoided by identifying patients with variant alleles before therapy and starting therapy at low dosages.     

Common urologic problems in children: guides to evaluation and referral, Part I

A discussion of common urologic problems in children is presented to provide primary physicians with appropriate guidelines for evaluation and referrals. The problems will be discussed in two parts: Part I will cover urinary tract infections, voiding dysfunctions, hematuria and proteinuria. Part II will cover abnormalities found on antenatal renal ultrasonography, hypospadias and other penile anomalies, phimosis, undescended testes, inguinal hernia and hydrocele, and varicoceles. An adage states: "The questions in medicine never change over time--only the answers." Certainly the busy primary care physician may experience the frustration of changing evaluation guidelines established by narrow subspecialties. Guidelines for the evaluation of children with disorders of the genitourinary tract are no exception. The following presentation will address some of the most common childhood urologic problems with a brief discussion of how to evaluate and when to refer for pediatric urologic consultation or management.     

The value of a scoring system for hypoxic ischaemic encephalopathy in predicting neurodevelopmental outcome

Abstract A numeric scoring system for the assessment of hypoxic ischaemic encephalopathy during the neonatal period was tested. The value of the score in predicting neurodevelopmental outcome at 1 y of age was assessed. Forty-five infants who developed hypoxic ischaemic encephalopathy after birth were studied prospectively. In addition to the hypoxic ischaemic encephalopathy score all but two infants had at least one cranial ultrasound examination. Thirty-five infants were evaluated at 12 months of age by full neurological examination and the Griffiths Scales of Mental Development. Five infants were assessed at an earlier stage, four who died before 6 months of age and one infant who was hospitalized at the time of the 12 month assessment. Twenty-three (58%) of the infants were normal and 17 (42%) were abnormal, 16 with cerebral palsy and one with developmental delay. The hypoxic ischaemic encephalopathy score was highly predictive for outcome. The best correlation with outcome was the peak score; a peak score of 15 or higher had a positive predictive value of 92% and a negative predictive value of 82% for abnormal outcome, with a sensitivity and specificity of 71% and 96%, respectively. For the clinician working in areas where sophisticated technology is unavailable this scoring system will be useful for assessment of infants with hypoxic ischaemic encephalopathy and for prognosis of neurodevelopmental outcome.