Broccoli sprout supplementation during pregnancy prevents brain injury in the newborn rat following placental insufficiency.

Chronic placental insufficiency and subsequent intrauterine growth restriction (IUGR) increase the risk of hypoxic-ischemic encephalopathy in the newborn by 40 fold. The latter, in turn, increases the risk of cerebral palsy and developmental disabilities. This study seeks to determine the effectiveness of broccoli sprouts (BrSp), a rich source of the isothiocyanate sulforaphane, as a neuroprotectant in a rat model of chronic placental insufficiency and IUGR. Placental insufficiency and IUGR was induced by bilateral uterine artery ligation (BUAL) on day E20 of gestation. Dams were fed standard chow or chow supplemented with 200mg of dried BrSp from E15 - postnatal day 14 (PD14). Controls received Sham surgery and the same dietary regime. Pups underwent neurologic reflex testing and open field testing, following which they were euthanized and their brains frozen for neuropathologic assessment. Compared to Sham, IUGR pups were delayed in attaining early reflexes and performed worse in the open field, both of which were significantly improved by maternal supplementation of BrSp (p<0.05). Neuropathology revealed diminished white matter, ventricular dilation, astrogliosis and reduction in hippocampal neurons in IUGR animals compared to Sham, whereas broccoli sprout supplementation improved outcome in all histological assessments (p<0.05). Maternal dietary supplementation with BrSp prevented the detrimental neurocognitive and neuropathologic effects of chronic intrauterine ischemia. These findings suggest a novel approach for prevention of cerebral palsy and/or developmental disabilities associated with placental insufficiency.

Scope of linear estimators of tidal and occluded volumes using thoracoabdominal indications of breathing movement coordination.

The basic theory for respiratory inductive plethysmography (RIP) applications was re-examined, refined and tested. A realistic model of the RIP interpretation of respiratory mechanics related tidal volumes (VT) to a linear combination of ribcage and abdomen movements. Lissajous plots of asynchronous thoracoabdominal movements revealed their net effect equivalent to the superposition of synchronous and antipathetic respiration modes at right angles, along the principal axes specific to the combined motion. Predictors of relative changes in VT, degree of asynchrony and volume thus being occluded were developed via least squares estimation theory, with an optional validation facility. The approach enabled clinically adequate analysis of 452 h of RIP data from 29 postoperative patients. Correct identification of only seven complete apnoeas in 111 incidences of obstruction during periodic, variable, asynchronous or paradoxical natural breathing was substantiated via non-invasive airflow monitoring. The modelling helped clarify RIP limitations--the possibility of misleading indications from obese or abnormal physiques or movement artefacts degrading its otherwise nearly optimal performance. Nevertheless, our uncalibrated predictors had better theoretical basis, improved reliability and more convenient practical utility than the traditional approach of calibrating RIP by spirometry prior to non-invasive monitoring and identifying and classifying apnoeas.

Assessing thoracoabdominal asynchrony.

The traditional method of derivation of phase difference between ribcage and abdomen breathing movements from a Lissajous plot is shown to be unsatisfactory for assessing the degree of asynchrony. The signal processing technique of cross-correlation is introduced as a better, statistically based approach. Even so, examination of the latent structure of a Lissajous figure leads to the concept of movement sum and difference components along its principal axes. This more general form of analysis is used for indicating relative changes in tidal volume during postoperative monitoring of Cheyne-Stokes breathing with obstructive apnoea, as well as tracking the degree of asynchrony. The theoretical and practical limitations of inductive plethysmography calibrations are such that the proposed methods of uncalibrated non-invasive respiratory monitoring are also preferable as research tools.

Progress in non-invasive respiratory monitoring using uncalibrated breathing movement components.

The theory for optimal linear combination of uncalibrated breathing movements was developed and applied in non-invasive respiratory monitoring situations for assessment. 16 patients were monitored overnight for respiratory depression during postoperative pain treatment. Intranasal/extra-oral airway pressure monitoring and pulse oximetry signals were recorded at 50 Hz. Respiratory inductive plethysmography (RIP) provided guidance to nurses regarding sensitivity settings of the pressure device during slow, shallow breathing, and vital information about breathing movements to help distinguish central from obstructive apnoeas. Subsequent analysis showed that the principal components of the standardized RIP signals would be helpful in any automated identification of pressure indicator false alarms and could provide a simple means for supplementary breath classification. The sum and difference of the scaled RIP values tracked changes in tidal volume and indicated any breathing movement asynchrony or paradox associated with obstructions. A construction was developed for emulating RIP calibration predictions of relative changes in tidal volume to within about 1%, so that invasive or demanding monitoring preparations could be by-passed altogether. The necessary signal combination and linearcalibration model background is reviewed for this simple formulation, which arises from component analysis and least squares regression. The methods are illustrated for definitive non-invasive postoperative monitoring and calibration situations. Theoretical and physiological reasons for preferring the use of balanced ribcage and abdomen contributions to overall tidal volume are presented that also help clarify the greater limitations of traditional RIP monitoring practices.

A systematic review of comparisons of effect sizes derived from randomised and non-randomised studies.

BACKGROUND: There is controversy about the value of evidence about the effectiveness of healthcare interventions from non-randomised study designs. Advocates for quasi-experimental and observational (QEO) studies argue that evidence from randomised controlled trials (RCTs) is often difficult or impossible to obtain, or is inadequate to answer the question of interest. Advocates for RCTs point out that QEO studies are more susceptible to bias and refer to published comparisons that suggest QEO estimates tend to find a greater benefit than RCT estimates. However, comparisons from the literature are often cited selectively, may be unsystematic and may have failed to distinguish between different explanations for any discrepancies observed. OBJECTIVES: The aim was to investigate the association between methodological quality and the magnitude of estimates of effectiveness by comparing systematically estimates of effectiveness derived from RCTs and QEO studies. Quantifying any such association should help healthcare decision-makers to judge the strength of evidence from non-randomised studies. Two strategies were used to minimise the influence of differences in external validity between RCTs and QEO studies: a comparison of the RCT and QEO study estimates of effectiveness of any intervention, where both estimates were reported in a single paper a comparison of the RCT and QEO study estimates of effectiveness for specified interventions, where the estimates were reported in different papers. The authors also sought to identify study designs that have been proposed to address one or more of the problems often found with conventional RCTs. DATA SOURCES: Relevant literature was identified from: The Cochrane Library, MEDLINE, EMBASE, DARE, and the Science Citation Index. References of relevant papers already identified experts. Electronic searches were very difficult to design and yielded few papers for the first strategy and when identifying study designs. CHOICE OF INTERVENTIONS TO REVIEW FOR STRATEGIES 1 AND 2: For strategy 1, any intervention was eligible. For strategy 2, interventions for which the population, intervention and outcome investigated were anticipated to be homogeneous across studies were selected for review: Mammographic screening (MSBC) of women to reduce mortality from breast cancer. Folic acid supplementation (FAS) to prevent neural tube defects in women trying to conceive. DATA EXTRACTION AND QUALITY ASSESSMENT: Data were extracted by the first author and checked by the second author. Disagreements were negotiated with reference to the paper concerned. For strategy 1, study quality was scored using a checklist to assess whether the RCT and QEO study estimates were derived from the same populations, whether the assessment of outcomes was 'blinded', and the extent to which the QEO study estimate took account of possible confounding. For strategy 2, a more detailed instrument was used to assess study quality on four dimensions: the quality of reporting, the generalisability of the results, and the extent to which estimates of effectiveness may have been subject to bias or confounding. All quality assessments were carried out by three people. DATA SYNTHESIS AND ANALYSIS: For strategy 1, pairs of comparisons between RCT and QEO study estimates were classified as high or low quality. Seven indices of the size of discrepancies between estimates of effect size and outcome frequency were calculated, where possible, for each comparison. Distributions of the size and direction of discrepancies were compared for high- and low-quality comparisons. FOR STRATEGY 2, THREE ANALYSES WERE CARRIED OUT: Attributes of the instrument were described by k statistics, percentage agreement, and Cronbach's a values. Regression analyses were used to investigate -variations in study quality. (ABSTRACT TRUNCATED)

Pulmonary blood flow measured by inspiratory inert gas concentration forcing oscillations.

The aim of this study was to discover if the forced inspired inert gas sinewave technique could be used to measure pulmonary blood flow, using nitrous oxide as the indicator gas, following inotropic stimulation of the heart by dobutamine, in the presence of a constant alveolar ventilation. Cardiac output (range 1-4.5 L min(-1)) was measured in six dogs by thermodilution and by calculation from the sinusoidal expired partial pressures of argon and nitrous oxide using: (i) analytical equations and a conventional continuous ventilation three-compartment lung model, which did not include recirculation; and (ii) a digital simulation tidal ventilation lung model (Gavaghan and Hahn, 1996. Respir. Physiol. 106, 209-221) which was adapted to include nitrous oxide mixed-venous recirculation from a combined single viscera compartment. The continuous ventilation model calculations always underestimated thermodilution cardiac output, with the bias error increasing to almost -1 L min(-1) at the longest forcing periods, 4-5 min. In contrast, the tidal ventilation model calculations were in close agreement to thermodilution cardiac output, with biases of -0.04 and -0.26 L min(-1) at forcing periods of 2 and 3 min, respectively.

Reporting of 'hypotension' after epidural analgesia during labour. Effect of choice of arm and timing of baseline readings.

We studied 20 women in labour to see how reporting 'hypotension' after obstetric epidural analgesia is affected by position of the blood pressure cuff and baseline definition. Blood pressure was recorded from both arms simultaneously while the woman was semirecumbent and then in the left lateral position. Three readings were then taken after epidural bupivacaine, one left lateral and the remainder right lateral. Before the epidural, blood pressure in the dependent arm in the lateral position was similar to blood pressure in either arm in the semirecumbent position and an average of 10 mmHg (systolic) and 14 mmHg (diastolic) higher than blood pressure in the uppermost arm (p < or = 0.00005). This difference persisted in both lateral positions as epidural analgesia became established. Choosing different definitions of hypotension, baselines and arm to measure blood pressure resulted in 'hypotension rates' between 0% and 75%. For blood pressure measurement in the lateral position, the blood pressure cuff should be placed on the dependent arm.

The effects of cardiopulmonary bypass temperature on neuropsychologic outcome after coronary artery operations: a prospective randomized trial.

UNLABELLED: The effect of systemic perfusion temperature on postoperative cognitive function was investigated in 96 adult patients undergoing elective coronary revascularization with cardiopulmonary bypass at 28 degrees C, 32 degrees C, or 37 degrees C. Neuropsychologic performance was assessed 1 day before the operation and 6 weeks after the operation. Five tests were adapted from the Wechsler Adult Intelligence Scale and two from the Wechsler Memory Scale. RESULTS: No patients had major neurologic complications. Ninety-three patients completed the five Wechsler Adult Intelligence Scale tests, but only 70 went on to complete the Wechsler Memory Scale tests as well. In these, there was an effect of cardiopulmonary bypass temperature on the number of neuropsychologic tests in which there was a preoperative to postoperative deterioration (p = 0.021), the number with bypass at 37 degrees C being significantly greater than the number with bypass at 32 degrees C (p = 0.015). Subsidiary analyses using a multivariate linear model examined the effect of cardiopulmonary bypass temperature on the magnitude of change, with or without allowing for other possible confounding influences. There was an adverse effect of normothermic (37 degrees C) versus moderately hypothermic (32 degrees C) perfusion---more convincingly displayed in the analyses of all seven scores rather than just the Wechsler Adult Intelligence Scale scores. Further cooling to 28 degrees C conferred no additional benefit in terms of cognitive function. The importance of the deterioration is open to question.

Disturbed mother-infant interaction in association with congenital heart disease.

OBJECTIVE: To investigate whether difficulties are experienced in the interaction between infants with congenital heart disease and their mothers and to identify infants who show compromised emotional development, in order to offer intervention during the early stages of postoperative compensatory growth. METHODS: 20 infants and their mothers were compared with 20 non-cardiac mother-infant pairs. Infants were filmed in interaction for 30 minutes two days before and six months after corrective surgery. Fifteen minutes of film were analysed in 180 5-s units. The emotional tone (affect) and the interpersonal engagement were classified as positive or negative by prespecified criteria. The percentages of positive scores were analysed. The mental health of the mothers was also assessed. RESULTS: Cardiac infants showed less positive affect and engagement than the noncardiac group at both sessions. There was no correlation between of positive affect or engagement and the severity of the condition in either group. Cardiac mothers showed less positive affect and engagement than the comparison group, and were psychologically distressed at both sessions. The engagement scores of the mothers of the cardiac infants were also more variable. CONCLUSIONS: Cardiac infants and their mothers have lower levels of positive affect and engagement than non-cardiac mother-infant pairs. Thus some mothers are unable to adapt to their infant. This leads to disordered interaction which is maintained at six months. This information can be used to offer intervention during the early stages of postoperative compensatory growth.

Patient-controlled epidural diamorphine for post-operative pain: verbal rating and visual analogue assessments of pain.

Twenty-two patients were studied while receiving epidural analgesia with diamorphine after major lower abdominal surgery under combined regional and general anaesthesia. Epidural PCA began when the intraoperative epidural block with bupivacaine wore off enough for the patient to request treatment. It was started with 2 mg of diamorphine and continued with a reducible background infusion that was initially set at 0.2 mg h-1 and supplemented by on-demand doses of 0.2 mg, with a lockout time of 15 min. The patients received routine post-operative monitoring and care, with pain at rest being assessed on a four-point verbal rating scale (VRS, none, mild, moderate, severe) at 5, 10, 15, 30, 45, 60, 90 and 120 min from the start of ePCA, then hourly until 24 h and then 2-hourly until 48 h. VRS on coughing and a 10 cm visual analogue score (VAS) at rest and on coughing were recorded at the same times at 4 h, then 4 hourly until 24 h and then at 48 h, at which times, blood samples were also taken to measure morphine concentrations by radioimmunoassay. Analgesia started promptly and reached a maximum at between 30 and 45 min, accompanied by maximum sedation. Thereafter clinically acceptable analgesia was maintained without undue sedation for 48 h, though pain on coughing was less well controlled than pain at rest. After the initial loading dose of diamorphine, the 95% confidence intervals (CI) for further consumption were 3.7 to 17 mg (average 9.7) in the first 24 h and 2.1 to 12.9 mg (average 6.7 mg) in the second 24 h. The plasma morphine concentrations rose to a plateau by about 15 min, with concentrations within 95% CI from 0 to 11 ng mliters-1 (average 5 ng mliters-1. The VRS and VAS pain scores were analysed by a conservative approach that treated them as ordinal data, and by a parametric approach that treated them as interval data. Both approaches conveyed broadly similar information about the post-operative analgesia.

Effects of cardiopulmonary bypass temperature on pulmonary gas exchange after coronary artery operations.

BACKGROUND: Pulmonary dysfunction is one aspect of the postoperative morbidity associated with cardiopulmonary bypass. Normothermic systemic perfusion can result in shorter intubation times, which have been attributed to improved pulmonary gas exchange, but the influence of perfusion temperature on pulmonary gas exchange itself is not known. METHODS: Pulmonary gas exchange was assessed using alveolar-arterial oxygen pressure gradients in 45 patients undergoing routine coronary revascularization who were randomized to undergo cardiopulmonary bypass at 28 degrees C, 32 degrees C, or 37 degrees C. This was part of a more comprehensive study of the effects of temperature on bodily systems. The gradients were estimated preoperatively with the patients breathing air, again over a period between 2 and 4 hours postoperatively during mechanical ventilation with three different oxygen concentrations (30%, 40%, and 60%), and again 1 hour after extubation while breathing the same three oxygen concentrations. RESULTS: Preoperative alveolar-arterial oxygen pressure gradients on air were 24.4 +/- 8.2 mm Hg (mean +/- standard deviation) (28 degrees C), 24.5 +/- 20.4 mm Hg (32 degrees C), and 20.5 +/- 9.5 mm Hg (37 degrees C). Postoperatively, during ventilation and after rewarming, the gradients increased with the increase in inspired oxygen fraction concentrations (30% to 60%) from 67.1 +/- 12.0 mm Hg to 193.1 +/- 30.5 mm Hg (28 degrees C), from 76.4 +/- 20.6 mm Hg to 246.7 +/- 47.7 mm Hg (32 degrees C), and from 79.0 +/- 18.0 mm Hg to 222.9 +/- 40.5 mm Hg (37 degrees C), respectively. A similar pattern was noted 1 hour after extubation, when the gradients increased from 72.4 +/- 12.5 mm Hg to 256.6 +/- 26.5 mm Hg (28 degrees C), from 75.7 +/- 13.9 mm Hg to 252.7 +/- 38.3 mm Hg (32 degrees C), and from 69.1 +/- 19.3 mm Hg to 253.1 +/- 33.0 mm Hg (37 degrees C). There were no significant differences in alveolar-arterial oxygen pressure gradient between the three groups during ventilation or after extubation. CONCLUSIONS: Cardiopulmonary bypass perfusion temperature does not influence alveolar-arterial oxygen pressure gradients in the first 12 hours after routine coronary artery bypass grafting in patients with uncompromised pulmonary and left ventricular function.

Epidural diamorphine infusions with and without 0.167% bupivacaine for post-operative analgesia.

Forty patients who underwent upper or mid-abdominal surgery were randomly allocated to receive a post-operative epidural infusion of 0.083 mg ml-1 of diamorphine in either 0.167% bupivacaine or 0.9% NaCl solution. The nursing staff, who were unaware of which solution was being infused, managed the patients' pain according to a standardized scheme. They adjusted the epidural infusion rates to 3, 5 or 7 ml h-1 according to the patient's hourly reports of pain on a four point verbal rating scale (none, mild, moderate or severe), aiming to use the lowest allowed infusion rate to prevent or reduce any pain that was more than mild. Additional analgesia was given as diclofenac 75 mg intramuscularly if the patients report moderate pain while on the highest infusion rate. The nurses were instructed to summon anaesthetic help if pain relief was still unsatisfactory after diclofenac, but this was never necessary. Diclofenac was needed by six patients receiving diamorphine in saline and one receiving diamorphine in bupivacaine (P < 0.05). The range of average hourly epidural infusion rates was constrained by design to between 3 and 7 ml h-1 but the median of these values was 5 ml h-1 in the diamorphine-saline group and 3.35 ml h-1 in the diamorphine-bupivacaine group (P < 0.02). In patients receiving diamorphine in saline, a median of 6 (range 0-16) of the 24 h reports were of more than mild pain, whereas in the diamorphine-bupivacaine group, the corresponding figures were 2 (range 0-13) (P < 0.02)).(ABSTRACT TRUNCATED AT 250 WORDS)

Epidural infusions of sufentanil with and without bupivacaine: comparison with diamorphine-bupivacaine.

The requirements for supplementary 3 ml epidural injections of bupivacaine 0.5% (top-ups) were used in a randomized double-blind study to compare the effects of five types of thoracic epidural infusions given at 2.5 ml h-1 for the first 24 h after major surgery to the upper abdomen in 99 patients and the lower abdomen in 72. The infusions were: bupivacaine 0.167% alone; diamorphine 0.167 mg ml-1 (0.417 mg h-1) in bupivacaine 0.167%; sufentanil 2 micrograms ml-1 (5 micrograms h-1) in 0.167% bupivacaine; sufentanil 4 micrograms ml-1 (10 micrograms h-1) in 0.167% bupivacaine; and sufentanil 4 micrograms ml-1 (10 micrograms h-1) in normal saline. The patients who had upper abdominal surgery were on average older than those having lower abdominal surgery and a larger proportion of them were female. They received on average fewer top-ups. After both upper and lower abdominal surgery, epidural infusions of bupivacaine alone required the most frequent supplementation (inter-quartile range 6-14 top-ups in 24 h) and the two sufentanil-bupivacaine mixtures required the fewest (interquartile range 0-12 top-ups in 24 h). The infusions of sufentanil without bupivacaine were significantly less effective than the sufentanil-bupivacaine mixtures after upper (but not lower) abdominal surgery. Although the two sufentanil-bupivacaine mixtures were indistinguishable in analgesic effectiveness after either upper or lower abdominal surgery, the lower (5 micrograms h-1) dose rate of sufentanil gave a significantly higher average breathing rate and lower average PaCO2 for the first 24 h after lower (but not upper) abdominal surgery. Blood samples were taken (as an afterthought) from 11 patients receiving sufentanil 10 micrograms h-1, just before the epidural infusion was stopped. The concentrations were mostly above the range for systemic analgesia, but below the values that would have been expected if a steady state had been achieved.

Assessment of cardiorespiratory function using oscillating inert gas forcing signals.

A theoretical model (Hahn et al. J. Appl. Physiol. 75: 1863-1876, 1993) predicts that the amplitudes of the argon and nitrous oxide inspired, end-expired, and mixed expired sinusoids at forcing periods in the range of 2-3 min (frequency 0.3-0.5 min-1) can be used directly to measure airway dead space, lung alveolar volume, and pulmonary blood flow. We tested the ability of this procedure to measure these parameters continuously by feeding monosinusoidal argon and nitrous oxide forcing signals (6 +/- 4% vol/vol) into the inspired airstream of nine anesthetized ventilated dogs. Close agreement was found between single-breath and sinusoid airway dead space measurements (mean difference 15 +/- 6%, 95% confidence limit), N2 washout and sinusoid alveolar volume (mean difference 4 +/- 6%, 95% confidence limit), and thermal dilution and sinusoid pulmonary blood flow (mean difference 12 +/- 11%, 95% confidence limit). The application of 1 kPa positive end-expiratory pressure increased airway dead space by 12% and alveolar volume from 0.8 to 1.1 liters but did not alter pulmonary blood flow, as measured by both the sinusoid and comparator techniques. Our findings show that the noninvasive sinusoid technique can be used to measure cardiorespiratory lung function and allows changes in function to be resolved in 2 min.

Measurement of dead-space in a model lung using an oscillating inspired argon signal.

In a model lung, airways dead-space can be accurately measured using a forced inspired oscillating argon signal, which varies sinusoidally about a mean concentration of 6% v/v with an amplitude of +/- 4% v/v. With sinusoid forcing periods longer than 120 seconds, and at a breathing rate of 13.4 breaths minute-1, the mean airways dead-space can be measured with a standard error of less than 5%. Sinusoid forcing periods shorter than 120 s provided inaccurate estimates of dead-space and so should not be used with this technique.

The pathophysiology and laboratory diagnosis of congenital portosystemic shunts in dogs.

Abstract Congenital portosystemic shunts generally arise as single vascular anomalies that cause the portal blood to bypass the liver and enter the systemic venous circulation directly. The liver is primarily affected, as it is deprived of perfusion by portal hepatotrophic factors such as insulin, glucagon, and amino acids. There is progressive hepatic atrophy, and as a consequence, dysfunction. Hepatic encephalopathy can result from increased levels of ammonia and gamma-aminobutyric acid within the systemic circulation. Variably toxic amines, captans and short chain fatty acids may act as false neurotransmitters. Hypoglycaemia will exacerbate the effects of these substances. Increased concentrations of ammonia and uric acid in the urine predispose to the precipitation of ammonium biurate crystals and the formation of calculi. Haematological changes include anaemia, microcytosis, hypoproteinaemia, leucocytosis, and coagulation abnormalities. Gastrointestinal effects are common. They may be displayed as anorexia, vomiting, ptyalism, pica, diarrhoea, or polyphagia. Most dogs are less than 1 year of age at initial presentation. Diagnosis from a laboratory viewpoint will involve a consideration of the history, clinical findings, haematology, serum biochemistry and urinalysis. If the findings are suggestive of a congenital portosystemic shunt, the demonstration of elevated fasting or, more consistently, post-prandial serum bile acid concentrations, and subsequent histological examination of a liver biopsy will provide a definitive diagnosis.