ESR or CRP? A comparison of their clinical utility.

OBJECTIVE: To review the normal reference values for erythrocyte sedimentation rate (ESR) and the significance of high values in the elderly, to re-examine the correlation, if any, between ESR and C-reactive protein (CRP) and to compare their utility and limitations for both health screening and clinical management of patients. METHODS: CRP and ESR were measured in 295 blood samples from male and female subjects in whom their family doctors had found no clinically significant symptoms nor abnormal physical sign and in whom all other pathology tests gave normal results. None had been hospitalised during at least a six-week period prior to the study. RESULTS: The results showed a mean ESR of 10 mm/1 h (range 0-25) in both males and females below the age of 40 yrs; this increased with age, to a mean of 18 mm (range 0-35) by 60 yrs in both men and women. In the CRP test, 95% of the samples in the >40 yrs group had CRP range of 0-18 mg/l compared with 0-10 mg/l in the younger subjects. The distribution plot of CRP results showed a left skew with mode at about 2 mg/l, whereas the equivalent ESR distribution shows a broad plateau with less skew. Thus, there was more overlapping of the numerical values for ESR and CRP in subjects younger than 40 yrs, as compared with those over 40 yrs old in whom the two sets of measurements were well separated. The relative utility of the two tests in clinical management of patients was also discussed. Different rates of increase and subsequent fall in the test results were shown over several weeks on a patient with an acute infection. Initially, both tests were increased, but after antibiotic therapy the CRP returned to normal indicating that remission had occurred, whereas the ESR remained high, indicating persistence of the infection. A subsequent dramatic increase in CRP to 180 mg/l confirmed the re-infection that had been indicated earlier by the ESR. After further antibiotic therapy CRP fell to normal, followed later by a slower reduction in ESR to a normal value for the patient's age. CONCLUSION: This study confirms that after the age of 40, there is an age-related elevation of ESR, increasing steadily, especially after age 60 yrs. CRP is also affected by age, but to a much less extent. ESR and CRP appear to be equally useful and reliable as a screening test. Accordingly, in deciding which test should be carried out account must be taken of their relative convenience and cost. However, when required as a clinical test in the management of patients with specific diseases both tests should be carried out in tandem.

Three dimensional optical imaging of blood volume and oxygenation in the neonatal brain.

Optical methods provide a means of monitoring cerebral oxygenation in newborn infants at risk of brain injury. A 32-channel optical imaging system has been developed with the aim of reconstructing three-dimensional images of regional blood volume and oxygenation. Full image data sets were acquired from 14 out of 24 infants studied; successful images have been reconstructed in 8 of these infants. Regional variations in cerebral blood volume and tissue oxygen saturation are present in healthy preterm infants. In an infant with a large unilateral intraventricular haemorrhage, a corresponding region of low oxygen saturation was detected. These results suggest that optical tomography may provide an appropriate technique for investigating regional cerebral haemodynamics and oxygenation at the cotside.

Three-dimensional whole-head optical tomography of passive motor evoked responses in the neonate.

Optical tomography has been used to reconstruct three-dimensional images of the entire neonatal head during motor evoked responses. Data were successfully acquired during passive movement of each arm on four out of six infants examined, from which eight sets of bilateral images of hemodynamic parameters were reconstructed. Six out of the eight images showed the largest change in total hemoglobin in the region of the contralateral motor cortex. The mean distance between the peak response in the image and the estimated position of the contralateral motor cortex was 10.8 mm. These results suggest that optical tomography may provide an appropriate technique for non-invasive cot-side imaging of brain function.

Postnatal adaptation of cerebral blood flow using near infrared spectroscopy in extremely preterm infants undergoing high-frequency oscillatory ventilation.

AIM: To determine cerebral blood flow using near infrared spectroscopy in extremely preterm infants undergoing high-frequency oscillatory ventilation during the first three days of life. Low cerebral blood flow has been associated with both intra-ventricular haemorrhage and periventricular leucomalacia. It is well established that cerebral blood flow increases over the first three days of life in extremely preterm infants who are conventionally ventilated with intermittent positive pressure ventilation. However, there is no information about cerebral blood flow in preterm babies undergoing high-frequency oscillatory ventilation. In addition, there are concerns that high-frequency oscillatory ventilation may be associated with an increased incidence of intra-ventricular haemorrhage in premature infants. METHODS: Thirteen appropriately grown, preterm infants of less than 28 wk gestation who were admitted to the neonatal unit at University College Hospital, London were studied using near infrared spectroscopy. Left ventricular output and right ventricular output were assessed echocardiographically. RESULTS: Extremely preterm infants undergoing high-frequency oscillatory ventilation have remarkably low cerebral blood flow in the first 12 h of life, median 6.7 (range 4.4-11) mls. 100 g(-1) min(-1) followed by an increase over the subsequent three days. Left ventricular output also increased over the first three days of life, whereas right ventricular output showed no clear relationship with time. Despite low cerebral blood flow only one infant had evidence of major cerebral injury. CONCLUSION: Cerebral blood flow is extremely low in this group of preterm babies. Despite this extremely low cerebral blood flow, the clinical outcome is good. There was an increase in cerebral blood flow and a corresponding increase in left ventricular output over the first few days of life.

Abnormal cerebral haemodynamics in perinatally asphyxiated neonates related to outcome.

AIM: To measure changes in cerebral haemodynamics during the first 24 hours of life following perinatal asphyxia, and relate them to outcome. METHODS: Cerebral blood volume (CBV), its response (CBVR) to changes in arterial carbon dioxide tension (PaCO(2)), and cerebral blood flow (CBF) were measured using near infrared spectroscopy (NIRS) in 27 term newborn infants with clinical and/or biochemical evidence consistent with perinatal asphyxia. RESULTS: Both CBF and CBV were higher on the first day of life in the infants with adverse outcomes, and a CBV outside the normal range had a sensitivity of 86% for predicting death or disability. The mean (SD) CBVR on the first day of life was 0.13 (0.12) ml/100 g/1/kPa, which, in 71% of infants, was below the lower 95% confidence limit for normal subjects. CONCLUSION: An increase in CBV on the first day of life is a sensitive predictor of adverse outcome. A reduction in CBVR is almost universally seen following asphyxia, but is not significantly correlated with severity of adverse outcome.

Low cerebral blood flow is a risk factor for severe intraventricular haemorrhage.

AIMS: To investigate the relation between cerebral blood flow on the first day of postnatal life and the severity of any subsequent germinal matrix haemorrhage-intraventricular haemorrhage (GMH-IVH). METHODS: Cerebral blood flow was measured in 24 babies during the first 24 hours of life using near infrared spectroscopy. Repeated cerebral ultrasound examination was performed to define the maximum extent of GMH-IVH. Infants were classified as: normal scan, minor periventricular haemorrhage (haemorrhage that resolved), or severe GMH-IVH (haemorrhage distending the ventricles, that progressed to either post haemorrhagic dilatation or porencephalic cyst formation). RESULTS: Cerebral blood flow was significantly lower in the infants with GMH-IVH (median 7.0 ml/100 g/min) than those without haemorrhage (median 12.2 ml/100 g/min), despite no difference in carbon dioxide tension and a higher mean arterial blood pressure. On subgroup analysis, those infants with severe GMH-IVH had the lowest cerebral blood flow. CONCLUSION: A low cerebral blood flow on the first day of life is associated with the subsequent development of severe intraventricular haemorrhage.

Regional hemodynamic responses to visual stimulation in awake infants.

This study presents the first measurements using near infrared spectroscopy of changes in regional hemodynamics as a response to a visual stimulus in awake infants. Ten infants aged 3 d to 14 wk viewed a checkerboard with a 5-Hz pattern reversal. The emitter and detector (optodes) of a near infrared spectrophotometer were placed over the occipital region of the head. Changes in concentration of oxy- and deoxyhemoglobin (Hbo2 and Hb) were measured and compared during 10-s epochs of stimulus on and off. A control group of 10 infants aged 18 d to 13 wk were examined with the same setup, but with the optodes over the frontoparietal region. In the test group the total hemoglobin concentration (Hbo2 + Hb) increased while the stimulus was on by a mean (+/-SD) of 2.51 (+/-1.48) micromol x L(-1). Nine out of 10 infants showed an Hbo2 increase, and 9 out of 10 an Hb increase related to the stimulus. There was no significant change in any of these parameters in the control group. The results imply that there is increased cerebral blood flow due to stimulation that is specific to the visual cortex and that infants, unlike adults, show increased cerebral oxygen utilization during activation that outstrips this hemodynamic effect. The study demonstrates that near infrared spectroscopy can be used as a practical and noninvasive method of measuring visual functional activation and its hemodynamic correlates in the awake infant.

Cerebral blood flow increases over the first three days of life in extremely preterm neonates.

AIM: To measure changes in cerebral haemodynamics over the first three days of life in very preterm infants with normal brains. METHODS: Eleven mechanically ventilated infants (median gestational age 26 weeks) without evidence of major abnormalities on cranial ultrasound examination were studied. Cerebral blood flow (CBF) and cerebral blood volume (CBV) were measured using near infrared spectroscopy at least twice over the first three days of life. RESULTS: Cerebral blood flow increased significantly with time (p = 0.02; stepwise linear regression) and this was independent of mean arterial blood pressure, PaCO2, and haematocrit. CONCLUSION: This change is likely to represent a normal adaptive response of the cerebral circulation to postnatal life.

Measurement of cranial optical path length as a function of age using phase resolved near infrared spectroscopy.

Near infrared spectroscopy (NIRS) has been used to measure concentration changes of cerebral hemoglobin and cytochrome in neonates, children, and adults, to study cerebral oxygenation and hemodynamics. To derive quantitative concentration changes from measurements of light attenuation, the optical path length must be known. This is obtained by multiplying the source/ detector separation by a laboratory measured differential path length factor (DPF) which accounts for the increased distance traveled by light due to scattering. DPF has been measured by time of flight techniques on small populations of adults and postmortem infants. The values for adults are greater than those for newborns, and it is not clear how to interpolate the present data for studies on children. Recent developments in instrumentation using phase resolved spectroscopy techniques have produced a bedside unit which can measure optical path length on any subject. We have developed an intensity modulated optical spectrometer which measures path length at four wavelengths. Two hundred and eighty three subjects from 1 d of age to 50 y were studied. Measurements were made at a fixed frequency of 200 MHz and a source detector separation of 4.5 cm. Results suggest a slowly varying age dependence of DPF, following the relation DPF690 = 5.38 + 0.049A0.877, DPF744 = 5.11 + 0.106A0.723, DPF807 = 4.99 + 0.067A0.814, and DPF832 = 4.67 + 0.062A0.819, where DPF690 is the DPF measured at 690 nm and A is age is expressed in years from full term. There was a wide scatter of values, however, implying that ideally DPF should be measured at the time of each study.

The noninvasive measurement of absolute cerebral deoxyhemoglobin concentration and mean optical path length in the neonatal brain by second derivative near infrared spectroscopy.

We have used second differential near infrared spectroscopy of water to determine the mean optical path length of the neonatal brain. By obtaining the ratio of the second differential features of deoxyhemoglobin to those of water, the absolute cerebral concentration of deoxyhemoglobin can be monitored continuously and noninvasively. Nineteen neonates were studied; the gestational age at birth varied from 23 to 38 wk, and the postconceptual age, when the spectra were recorded, ranged from 35 to 48 wk. The calculated mean deoxyhemoglobin concentration was 14.6 +/- 4.0 microM; the differential path length factor (mean optical path length/optode separation) calculated from the water peak at 730 nm was 4.66 +/- 1.01, and that calculated at the 830-nm peak was 3.91 +/- 0.75. These values are consistent with path length measurements using laser time-of-flight spectroscopy on postmortem neonates and phase-resolved spectroscopy on live neonates. Induced arterial oxygen saturation decreases from 98 to 93% showed no significant change in the mean optical path length, despite significant cerebral desaturation. Changes in the deoxyhemoglobin concentration after this procedure were identical, whether measured by second differential analysis at 760 nm or by multilinear regression over the wavelength range 740-900 nm. When combined with existing methods of measuring total cerebral hemoglobin concentration, second differential near infrared spectroscopy can be used to derive the mean cerebral oxygen saturation. A preliminary experiment outlined the feasibility of this approach and yielded a saturation value of 63%, consistent with near infrared sampling of a predominantly venous pool in the brain.

Regional changes in cerebral haemodynamics as a result of a visual stimulus measured by near infrared spectroscopy.

Near infrared spectroscopy (NIRS) is used to measure global changes in cerebral haemodynamics. We have adapted the technique to measure regional changes in response to a visual stimulus. Ten volunteers were exposed to a computer generated visual stimulus designed to activate a large area of the visual cortex, including V1, V2, V3, V4 and V5. The stimulus was on for 30 s and off for 30 s. Changes in the concentrations of oxyhaemoglobin ([HbO2]) and deoxyhaemoglobin ([Hb]) were measured using a commercial spectrometer (NIRO500), over the occipital cortex. The data were summed over ten cycles. As a control, the experiment was repeated over the frontal cortex. For each subject [HbO2] increased during stimulation, and decreased when the stimulus was off. The mean (+/- s.e.m.) change in [HbO2] was 0.54 +/0 0.14 micromol 1(-1). The change in total haemoglobin concentration, given by [HbO2] + [Hb] was 0.61 +/- 0.21 micromol 1(-1), equivalent to a rise in cerebral blood volume of 0.04 +/- 0.01 ml 100 g(-1) which is about 2% of the total cerebral blood volume. There was no significant change in [HbO2] over the frontal cortex, implying that the changes in blood volume originated in the occipital lobe. This demonstrates that NIRS provides a non-invasive method of measuring regional changes in cerebral haemodynamics as a result of visual stimulation.

Optical pathlength measurements on adult head, calf and forearm and the head of the newborn infant using phase resolved optical spectroscopy.

We have used an intensity modulated optical spectrometer, which measures the phase shift across tissue experienced by intensity modulated near-infrared light, to determine the absolute optical pathlength through tissue. The instrument is portable and takes only 5 s to record pathlength at four wavelengths (690 nm, 744 nm, 807 nm and 832 nm). The absolute pathlength divided by the known spacing between the light source and detector on the skin is the differential pathlength factor (DPF) which previous studies have shown is approximately constant for spacings greater than 2.5 cm. DPF results are presented for measurements on 100 adults and 35 newborn infants to determine the statistical variation on the DPF. All measurements were made at a frequency of 200 MHz with source-detector spacings of > 4 cm. Results at 807 nm show a DPF of 4.16(+/- 18.8%) for adult arm, 5.51(+/- 18%) for adult leg, 6.26(+/- 14.1%) for adult head and 4.99(+/- 9%) for the head of a newborn infant. A wavelength dependence was obtained for DPF on all tissues and a difference in DPF between male and female was observed for both the adult arm and leg. The results can be used to improve the quantitation of chromophore concentration changes in adults and newborn infants.

Reversal of hepatic encephalopathy and alteration in amino acid profiles after blocking a surgical splenorenal shunt by interventional radiological techniques.

Portal-systemic shunts are effective in preventing haemorrhage from varices in portal hypertension, but at the price of hepatic encephalopathy. We describe the blockage of a splenorenal shunt using interventional radiology, in a patient with incapacitating chronic encephalopathy. The procedure successfully reversed encephalopathy, without haemodynamic disturbances or haemorrhage from recurrent varices and was associated with a return of the plasma amino acid profile towards normal, with a reduction in aromatic amino acids and an increase in branch chain amino acids. This observation supports the hypothesis that changes in plasma amino acid profiles in patients with portal-systemic shunting are due to the diversion of portal blood rather than the underlying chronic liver disease.

Avoidable accumulation of potentially toxic levels of benzothiazoles in babies receiving intravenous therapy.

Large amounts of a compound of exogenous origin were present in the serum of premature babies receiving prolonged intravenous therapy. This compound, identified as 2-(carboxymethylthio)benzothiazole (CMB) is derived from oxidation of 2-(hydroxyethylthio)benzothiazole which is leached out of rubber components of intravenous administration sets and syringes. Serum concentrations of CMB after prolonged exposure can exceed 500 mumol/l; concentrations over 35 mumol/l were observed in 91 babies over a period of twenty-seven months. This potentially toxic accumulation can be largely avoided by judicious choice of equipment.

Renal clearance of amino acids in pregnancy complicated by preeclampsia.

Renal clearance of most amino acids was increased in the third trimester of pregnancy. The greatest change was with glycine, where clearance increased thirteen-fold and the plasma level decreased. No difference in renal clearance of amino acids was demonstrated in four patients with proteinuric hypertension when compared with that in normal pregnancy. Progesterone, given to non-pregnant women, caused a fall in mean plasma glycine. This was associated with increased renal clearance in 2 out of 3 women, and indicates that progesterone may contribute to the increased renal excretion of some amino acids in pregnancy, probably acting selectively on tubular reabsorption.

A prospective study of intrapulmonary fat accumulation in the newborn lung following intralipid infusion.

In order to assess the safety and stability of a parenteral fat emulsion (Intralipid) in total parenteral nutrition (TPN), 29 infants were infused Vamin glucose and Dextrose electrolyte solution as well as one of two isocaloric regimens; either 25% Dextrose (Group I) or 10% Intralipid (Group II). Regular biochemical monitoring was performed in all cases and no infants became lipaemic nor developed abnormally high levels of total free fatty acid. Eight infants died and only those who had received fat emulsion had lipid staining material distending the pulmonary vessels. One infant having low infusion rates of Intralipid had massive fat accumulation in the lungs, but biochemistry during life had been normal. We speculate that in ill infants the emulsion becomes less stable and agglomeration of fat particles occurs which are then fully filtered out by the lungs before metabolism of the exogenous fat can occur.

Caffeine, theophylline and theobromine in pregnancy.

Dietary surveys estimated the caffeine intake of pregnant women in London to average 1.4 mmol (270 mg) with a range of 0 to 6.0 mmol (0-1160 mg)/day. The average plasma caffeine was 6.5 (SD 2.8-14.8), plasma theophylline 2.9 (SD 1.3-6.7), plasma theobromine 2.1 (SD 0.9-4.9) mumol/l. The results of the dietary surveys showed a fair correlation (r = 0.59; p less than 0.01) with plasma caffeine levels, but the surveys are best regarded as a basis for counseling rather than an accurate estimate of intake.

Bronchial hypersecretion in preterm neonates.

During an 18-month period, 11 preterm infants with birthweights between 700 and 1560 g (mean 1.2 kg) developed excessive tracheobronchial secretions during intensive care. No single obstetric factor was incriminated. Copious, viscous, tracheobronchial secretions were noted at about 5 days during mechanical ventilation via endotracheal tube causing recurrent segmental collapse, hypoxia, and hypercapnia (median peak PCO2 13.5 kPa). All infants were treated with frequent bronchial lavages and continued intermittent positive pressure ventilation, together with high concentrations of oxygen. No infant died, but morbidity was high. Tracheostomy was performed on 2 infants (one at age 3 months, because of severe croup) and 2 others had clinical or physiological evidence of upper airways narrowing. Follow-up studies showed that this group had more problems of airways obstruction throughout the first year of life as well as increased lung stiffness. The hypersecretion group showed a higher incidence of chronic lung disease. Likely aetiological factors were sought. Contamination of the mechanical ventilation equipment by detergent and activated glutaraldehyde was found; this could have been a contributory factor.