Body mass index of girls in health influences menarche and skeletal maturation: a leptin-sympathetic nervous system focus on the trunk with hypothalamic asymmetric dysfunction in the pathogenesis of adolescent idiopathic scoliosis?

Lower body mass index (BMI) and lower circulating leptin levels have been reported in girls with AIS. In this paper we evaluate skeletal sizes and asymmetries by higher and lower BMI subsets about the means for each of three groups of girls age 11-18 years: 1) normals, 2) school screening referrals, and 3) preoperative girls. Higher and lower BMI subsets, likely to have separated subjects with higher from those with lower circulating leptin levels, identify: 1) girls with relatively earlier and later menarche; 2) trunk width size greater in the higher than in the lower BMI subset, of all three groups; 3) abnormal upper arm length (UAL) asymmetries (right minus left) in the lower BMI subset of the preoperative girls; and 4) in thoracic AIS of screened and preoperative girls, Cobb angle and apical vertebral rotation each significantly and positively correlate with UAL asymmetry in the lower BMI subset but not in the higher BMI subset. In preoperative girls, the lower BMI subset shows the combination of relatively reduced pelvic width and abnormal UAL asymmetry, suggesting that both are linked to lower circulating leptin levels. An earlier puberty with hormonal changes provides a plausible explanation for the larger trunk width at the shoulders and pelvis especially at the younger ages in the higher BMI subsets. At the shoulders, this widening is driven by the ribcage which, in human evolution was acquired with decoupling of head and trunk movements required for efficient bipedal gait. The UAL asymmetry patterns within the groups and BMI subsets are not explained by hormonal mechanisms. It is hypothesized that 1) normal trunk widening of the thoracic cage by hormones in human adolescence is supplemented via the sympathetic nervous system under leptin-hypothalamic control influenced by energy stores (metabolic fuel); and 2) hypothalamic dysfunction with altered hypothalamic sensitivity to leptin through a SNS-driven asymmetric effect may create skeletal length asymmetries in upper arms, ribs, ilia and vertebrae, and initiate AIS. Additional mechanisms acting in the spine and trunk may be required for AIS to progress including 1) somatic nervous system dysfunction, 2) biomechanical spinal growth modulation, and 3) osteopenia.

Ultrasound femoral anteversion (FAV) relative to tibial torsion (TT) is abnormal after school screening for adolescent idiopathic scoliosis (AIS): evaluation by two methods.

In the scoliotic spine, torsion is generally evaluated in relation to axial rotation of the apical vertebra. In the lower limbs, the changes in torsion by age of femoral anteversion (FAV) relative to tibial torsion (TT) have been studied in dried bones, normal growing subjects and adults and subjects with osteoarthritis of the hip or the knee. This paper reports the application of real-time ultrasound to FAV and TT in normal children age 11-18 years and in scoliosis screening referrals with particular reference to how FAV relates to TT as 1) ratios, and 2) tibio-femoral index (TFI) of torsion, calculated as TT minus femoral FAV. The FAV/TT ratio findings show an abnormal normal relationship of FAV to TT both proximo-distally and in left-right asymmetry. These may express torsional abnormalities in femoral and/or tibial growth plates with left-right asynchrony suggesting the possibility of similar torsional abnormalities in vertebral end-plates and/or rib growth plates initiating the deformity of AIS. TFI of the right limb in the scoliosis girls is greater than in the normals that is interpreted as resulting from earlier skeletal maturation of FAV. FAV/TT ratios and TFI are unrelated to the spinal deformity (Cobb angle and apical vertebral rotation) except for boys where TFI is associated with apical vertebral rotation. FAV/TT ratios may be a more accurate method estimating the relationship of FAV to TT. than TFIs.

Leg-arm length ratios correlate with severity of apical vertebral rotation in girls after school screening for adolescent idiopathic scoliosis (AIS): a dynamic pathomechanism in the initiation of the deformity?

There is increasing support for the view that the unique human bipedalism and the erect posture are prerequisites for the pathogenesis of adolescent idiopathic scoliosis (AIS). How human bipedalism may contribute to the pathogenesis of AIS is not clear. In normal humans, axial rotations and counter-rotations of the trunk are carried out frequently and forcibly in activities that are not performed by quadrupeds. Some workers have analysed gait in AIS subjects, others have studied torsions in lower limb bones, but there are only two reports on leg-arm ratios in relation to AIS. In this paper, leg-arm ratios studied in relation to the spinal deformity in scoliosis screening referrals, reveal a highly significant correlation with the apical vertebral rotation but not the Cobb angle of the scoliosis curves. We suggest that leg-arm proportions and movements during gait involving pelvi-spinal axial rotations and thoracic counter-rotations contribute a dynamic pathomechanism to early AIS from whatever cause and involving the thoracic cage. Curve progression needs other mechanisms that may include a central nervous system failure to control structural asymmetry of vertebral axial rotation, and biomechanical spinal growth modulation.

Ultrasound femoral anteversion (FAV) and tibial torsion (TT) after school screening for adolescent idiopathic scoliosis (AIS).

Torsion and counter-torsion in the spine are features of the three-dimensional deformity of adolescent idiopathic scoliosis, Vertebral axial rotation has recently been found in the normal adult thoracic spine. Torsion in the lower limbs, femora and tibiae is a feature of normal human skeletal postnatal development. In recent years, femoral anteversion (FAV) and tibial torsion (TT) have been studied in normal children by imaging techniques, especially ultrasound. This paper reports summaries of the application of real-time ultrasound to FAV and TT of normal children and scoliosis school screening referrals. In the scoliosis girls and boys, the FAV decrease and FAV asymmetry compared with normals may result from abnormally increased femoral detorsion maturationally earlier with left-right asynchrony which, if repeated as a growth plate anomaly in the trunk (spine and/or periapical ribs), might initiate the AIS deformity, given other requirements. In scoliosis boys relative to girls, the TT decrease without asymmetry may result from sexually dimorphic maturation at knee tibial growth plates ? maturationally delayed TT with left-right synchrony.

The posterior skeletal thorax: rib-vertebral angle and axial vertebral rotation asymmetries in adolescent idiopathic scoliosis.

The deformity of the ribcage in thoracic adolescent idiopathic scoliosis (AIS) is viewed by most as being secondary to the spinal deformity, though a few consider it primary or involved in curve aggravation. Those who consider it primary ascribe pathogenetic significance to rib-vertebra angle asymmetry. In thoracic AIS, supra-apical rib-vertebra angle differences (RVADs) are reported to be associated with the severity of the Cobb angle. In this paper we attempt to evaluate rib and spinal pathomechanisms in thoracic and thnoracolumbar AIS using spinal radiographs and real-time ultrasound. On the radiographs by costo-vertebral angle asymmetries (rib-vertebral angle differences RVADs, and rib-spinal angle differences RSADs), apical vertebral rotation (AV) and apical vertebral translation (AVT) were measured; and by ultrasound, spine-rib rotation differences (SRRDs) were estimated. RVADs are largest at two and three vertebral levels above the apex where they correlate significantly and positively with Cobb angle and AVT but not AVR. In right thoracic AIS, the cause(s) of the RVA asymmetries is unknown: it may result from trunk muscle imbalance, or from ribs adjusting passively within the constraint of the fourth column of the spine to increasing spinal curvature from whatever cause. Several possible mechanisms may drive axial vertebral rotation including, biplanar spinal asymmetry, relative anterior spinal overgrowth, dorsal shear forces in the presence of normal vertebral axial rotation, asymmetry of rib linear growth, trunk muscle imbalance causing rib-vertebra angle asymmetry weakening the spinal rotation-defending system of bipedal gait, and CNS mechanisms.

Patterns of extra-spinal left-right skeletal asymmetries in adolescent girls with lower spine scoliosis: relative lengthening of the ilium on the curve concavity & of right lower limb segments.

Extra-spinal skeletal length asymmetry have been reported for the upper limbs and periapical ribs of patients with thoracic adolescent idiopathic scoliosis. This paper reports (1) a third pattern with relative lengthening of the ilium on the concavity of lower spine scolioses, and (2) a fourth pattern of relative lengthening of the right total leg and right tibia unrelated statistically to the severity or side of lower spinal scolioses. The findings pose the question: are these anomalous extra-spinal left-right skeletal length asymmetries unconnected with the pathogenesis of AIS. Or, are they indicative of what may also be happening to some vertebral physes as an initiating pathogenic mechanism for the scoliosis?

Left-right upper arm length asymmetry associated with apical vertebral rotation in subjects with thoracic scoliosis: anomaly of bilateral symmetry affecting vertebral, costal and upper arm physes?

Left-right skeletal length asymmetries in upper limbs related to curve side and severity have been detected with adolescent idiopathic scoliosis (AIS). This paper reports upper arm length asymmetry in thoracic scoliosis related significantly to apical vertebral rotation in school screening referrals. The reason(s) for the association of upper arm length asymmetry with apical vertebral rotation is unknown and three factors are considered: (1) neuromuscular mechanisms from primary or secondary causes, (2) relative concave neurocentral synchondrosis overgrowth, and (3) relative concave periapical rib length overgrowth, A putative anomaly of growth plates (physes) of ribs, neurocentral synchondroses and upper arms, would account for the findings. A solution to this dilemma may emerge from the results of surgery should concave periapical rib resections become evaluated further for right thoracic AIS in girls.

Etiologic theories of idiopathic scoliosis: neurodevelopmental concept of maturational delay of the CNS body schema ("body-in-the-brain").

Several workers consider that the etiology of adolescent idiopathic scoliosis (AIS) involves undetected neuromuscular dysfunction. During normal development the central nervous system (CNS) has to adapt to the rapidly growing skeleton of adolescence, and in AIS to developing spinal asymmetry from whatever cause. Examination of evidence from (1) anomalous extra-spinal left-right skeletal length asymmetries, (2) growth velocity and curve progression, and (3) the CNS body schema, parietal lobe and temporoparietal junction, led us to propose a new etiologic concept namely of delay in maturation of the CNS body schema during adolescence. In particular, the development of an early AIS deformity at a time of rapid spinal growth the association of CNS maturational delay results in the CNS attempting to balance a lateral spinal deformity in a moving upright trunk that is larger than the information on personal space (self) already established in the brain by that time of development. It is postulated that the CNS maturational delay allows scoliosis curve progression to occur - unless the delay is temporary when curve progression would cease. The putative maturational delay in the CNS body schema may arise (1) from impaired sensory input: (2) primarily in the brain; and/or (3) from impaired motor output. Oxidative stress with lipid peroxidation in the nervous system may be involved in some patients. The concept brings together many findings relating AIS to the nervous and musculo-skeletal systems and suggests brain morphometric studies in subjects with progressive AIS.

Patterns of extra-spinal left-right skeletal asymmetries and proximo-distal disproportion in adolescent girls with lower spine scoliosis: ilio-femoral length asymmetry & bilateral tibial/foot length disproportion.

Anomalous extra-spinal left-right skeletal length asymmetries have been detected in girls with adolescent idiopathic (AIS) in four sites (1) upper limbs, (2) periapical ribs, (3) ilium, and (4) right leg and right tibia. This paper on adolescent girls with lower spine scoliosis reports (1) a fifth pattern of left-right ilio-femoral length asymmetry associated with sacral alar height asymmetry, and (2) bilateral anomalous lengthening of the tibia relative to the foot. The findings are consistent with the hypothesis that at the time of diagnosis of AIS in girls there are anomalies of skeletal proportions associated with a predisposition to curve progression; these proportions are in three dimensions--left-right, cephalo-caudal in the trunk (proximo-distal in the lower limbs), and front-back in the trunk. The origin of these anomalies is unknown but possible causes, and of the associated AIS, are genetic and environmental factors acting in embryonic life not expressed phenotypically until years after birth.

Etiologic theories of idiopathic scoliosis: the breaking of bilateral symmetry in relation to left-right asymmetry of internal organs, right thoracic adolescent idiopathic scoliosis (AIS) and vertebrate evolution.

In the search to understand the etiology and pathogenesis of adolescent idiopathic scoliosis (AIS) some workers have focused on mechanisms initiated in embryonic life including a disturbance of bilateral (left-right or mirror-image) symmetry highly conserved in vertebrates. The normal external bilateral symmetry of vertebrates results from a default process involving mesodermal somites. The normal internal asymmetry of the heart, major blood vessels, lungs and gut with its glands is also highly conserved among vertebrates. It results from the breaking of the initial bilateral symmetry by a binary asymmetry switch mechanism producing asymmetric gene expression around the embryonic node and/or in the lateral plate mesoderm. In the mouse this switch occurs during gastrulation by cilia driving a leftward flow of fluid and morphogen(s) at the embryonic node (nodal flow) that favors precursors of the heart, great vessels and viscera on the left. Based on the non-random laterality of thoracic AIS curves, the hypothesis is suggested that an anomaly of the binary asymmetry switch explains the excess of right/left thoracic AIS. Some support for this hypothesis is the prevalence of right and left scoliosis curve laterality associated with situs inversus. There is recent evidence that vertebrates within their bilateralised shell retain an archaic left-right asymmetric visceral body organization evident in thoracic and abdominal organs.

Etiologic theories of idiopathic scoliosis: enantiomorph disorder concept of bilateral symmetry, physeally-created growth conflicts and possible prevention.

The detection of anomalous extra-spinal left-right skeletal length asymmetries in the upper limbs, periapical ribs, ilia and lower limbs of subjects with adolescent idiopathic scoliosis (AIS) raises questions about skeletal bilateral symmetry of vertebrates in health and disorder, its origin and control. The vertebrate body plan externally has mirror-image bilateral symmetries that are highly conserved culminating in the adult form. The normal human body can be viewed as containing paired skeletal structures in the axial and appendicular skeleton as 1) separate left and right paired forms (eg long limb bones, ribs, ilia), and 2) united in paired forms (eg vertebrae, sternum, skull, mandible). Each of these separate and united pairs are mirror-image forms--enantiomorphs. Left-right asymmetries of growth plates (physes) may cause (1) in long bones length asymmetries, (2) within one or more vertebral physes putative growth conflict with distortion as deformity, and (3) between ribs and vertebrae putative growth conflict that triggers thoracic AIS suggesting preventive surgery on spine and ribs. There is evidence of a possible role for environmental factors in AIS development. Genes and the environment (nature/nurture) may interact pre- and/or post-natally to explain both the deformity of AIS and its association with widespread anomalous skeletal length asymmetries. If substantiated there may ultimately be a place for the prevention of AIS in some subjects.

Spine-rib rotation differences at the apex in preoperative patients with adolescent idiopathic scoliosis: evaluation of a three-level ultrasound method.

This paper evaluates a new real-time ultrasound method to assess the difference between axial spinal (laminal) rotation and rib rotation at the apex of the scoliosis curve. An Aloka SSD 500 portable ultrasound machine with a veterinary long (172mm) 3.5 MHz linear array transducer was used to assess the reproducibility of the method in 13 preoperative patients with AIS. With the subject in a prone position and her head supported, readings of laminal and rib rotation were made directly on the back at 18 and 12 levels respectively The subject was repositioned after walking around the room and a second set of spinal and rib rotations obtained (repeats). All the readings were made by one observer (ASK). After plotting on graphs three levels of maximal difference between spine rotation and rib rotation about the apex were chosen visually by one observer (RGB) for which the mean apical spine-minus-rib rotation difference (SRRD) was calculated for each repeat. Findings for apical SRRDs. The mean apical SRRDs for the two repeats are 7.1 degrees and 6.9 degrees (range 2-18 degrees) with coefficients of variation of 49% and 62% respectively. Reproducibility. Graphic representation of spinal and rib rotation by 12 levels shows a fairly good agreement between repeats for most subjects. Spinal rotation is always greater than rib rotation. A paired t-test for the mean apical SRRD of the repeats shows no significant difference. Linear regression analysis of the mean apical SRRD repeats correlate significantly (r=0.70, P=0.008) with a residual mean square of 6.9 degrees (rms = 2.6 degrees). The technical error of the measurement (TEM) is 2.3 degrees and coefficient of reliability (R) 0.66. Conclusions. Real-time ultrasound can assess the difference between spinal and rib rotation about the apex of the scoliosis curve without the altered position detectably affecting the findings. The error (2-3 degrees) is high relative the mean apical SRRD (6-7 degrees). The apical SRRD findings have relevance to the pathogenesis of AIS.

Preliminary study of a new real-time ultrasound method for measuring spinal and rib rotation in preoperative patients with adolescent idiopathic scoliosis.

A portable ultrasound machine with a linear array transducer was used by one observer (ASK) to evaluate the reproducibility for each of spinal (laminal) rotation and rib rotation in 13 preoperative patients with AIS (thoracic 7, thoracolumbar 6, mean Cobb angle 50 degrees, right 9, left 4, age 15.4 years, girls 10). With the subject in a prone position and her head supported, readings of spinal (laminal) and rib rotations were made directly on the back at 18 and 12 levels respectively. The subject was repositioned after walking around the room and a second set of spinal and rib rotations obtained (repeats). Conclusious. Repositioning the patient significantly alters some single level readings of lam inal rotation and rib rotation. Although the mean average spinal rotation and rib rotation each have acceptable reproducibility, repositioning the patient significantly alters the findings. In the appraisal of surgery by ultrasound the positional change reported here for (I) single level laminal rotation and rib rotation, and (2) mean average rotation imposes caution on the interpretation of the findings. The method enables the axial spine-nh rotation differences to be evaluated which is the subject of a separate paper.

Anterior universal spine system for adolescent idiopathic scoliosis: a follow-up study using scoliometer, real-time ultrasound and radiographs.

Nine patients with AIS treated surgically with anterior USS instrumentation were examined by several methods pre-operatively and at each of 8 weeks, 1 year and 2 years after surgery (mean age 14.6 years, girls 7, boys 2, thoracolumbar 7, lumbar 1, thoracic 1, left 7, right 2). The methods used were (1) Scoliometer to measure angle of trunk inclinations (ATIs) in the standing forward bending position at each of 10 levels and converted to 18 levels by a computer program, (2) real-time ultrasound in the prone position of laminal rotations at each of 1 8 levels from TI-SI, and (3) anteroposterior radiographs in the standing erect position measured for each of Cobb angle, segmental vertebral rotation (Perdriolle) and segmental vertebral translation from the Ti-Si line (horizontal translation of each vertebral centroid from the T1-S1 line). The findings were plotted graphically and segmentally for each of Scoliometer ATJs, ultrasound laminal rotations, and radiographic vertebral rotations and translations. Findings. Graphical representation of the data shows that the improvement brought about by surgery is most clearly and consistently evident for segmental vertebral translation. The statistical analysis shows that the radiological parameters (Cobb angle, apical vertebral rotation and apical vertebral translation) and ultrasound spinal (laminal) rotation do not change detectably in follow-up. The Scoliometer ATI findings show an increase from 4 degrees (at 8 weeks) to 7 degrees (at 2 years) which is statistically significant. The evidence from this small sample of patients is consistent with the view that the compared with posterior USS, anterior USS surgery for AIS results in (1) similar initial rib hump correction, and (2) less rib hump reassertion during follow-up. More data are needed to evaluate these views.

The early detection of adolescent idiopathic scoliosis in three positions using the scoliometer and real-time ultrasound: should the prone position also be used?

The standing forward bending position is in general use for the early detection of adolescent idiopathic scoliosis. It also reveals humps caused by leg-length inequality and for this reason some workers have advocated using the sitting forward bending position. Most recently the prone position has been evaluated and even recommended. The introduction of B-mode and subsequently real-time ultrasound to measure rib rotation and spinal rotation has involved using the prone position. The numerical description of back humps in scientific studies requires measurements at several levels on the back from T1-S1. This paper utilizes 30 subjects referred by school screening for scoliosis from whom 10-level Scoliometer Angle of Trunk Inclinations (ATIs) were obtained twice in each of three positions--standing forward bending, sitting forward bending and prone. The ATIs were converted to 18 levels and (1) analysed for reproducibility, (2) compared in the three positions, and (3) compared with real-time ultrasound data of rib rotation obtained in the prone position. Several statistical methods are used. The reproducibility is best in the sitting and prone positions. While the prone position produces lower ATI readings, R squared values are significantly higher and Residual Mean Square (RMS) values significantly lower than those for each of the standing and sitting forward bending positions. Though the prone position has clear advantages, it is not advocated in clinical practice for various reasons. More research is needed. The evidence supports the view that the sitting forward bending position has advantages for the early detection of adolescent idiopathic scoliosis.

Back shape assessment in each of three positions in preoperative patients with adolescent idiopathic scoliosis: evaluation of a 10-level Scoliometer method interpolated to 18-levels.

A Scoliometer was used by one observer (RKP) to assess the reproducibility of angle of trunk inclinations (ATIs) in 13 preoperative patients with AIS (thoracic 7, thoracolumbar 6, mean Cobb angle 50 degrees, right 9, age 15.4 years, girls 10). Three positions were used namely standing forward-bending, (FB) sitting FB and prone. Readings of ATI on the back were obtained at each of 10 levels (T1-S1). The subject was repositioned after walking around the room and a second set of readings obtained (repeats). All readings were converted by a computer program to 18 levels and plotted. The readings from 18 levels were analysed by level, as well as summated and averaged both without and with correction for the side of the curve. Conclusions. Back surface asymmetry measured with a Scoliometer in these preoperative patients with AIS is less in the prone position than in each of the forward bending positions. The standing FB position has the best reproducibility which supports the practice of using this position to measure Scoliometer ATIs in preoperative patients with AIS.

The Ontario trial of active compression-decompression cardiopulmonary resuscitation for in-hospital and prehospital cardiac arrest.

OBJECTIVE: To compare the impact of active compression-decompression (ACD) cardiopulmonary resuscitation (CPR) and standard CPR on the outcomes of in-hospital and prehospital victims of cardiac arrest. DESIGN: Randomized controlled trial with blinding of allocation using a sealed container. SETTINGS: (1) Emergency departments, wards, and intensive care units of 5 university hospitals and (2) all locations outside hospitals in 2 midsized cities. PATIENTS: A total of 1784 adults who had cardiac arrest. INTERVENTION: Patients received either standard or ACD CPR throughout resuscitation. MAIN OUTCOME MEASURES: Survival for 1 hour and to hospital discharge and the modified Mini-Mental State Examination (MMSE). RESULTS: All characteristics were similar in the standard and ACD CPR groups for the 773 in-hospital patients and the 1011 prehospital patients. For in-hospital patients, there were no significant differences between the standard (n = 368) and ACD (n = 405) CPR groups in survival for 1 hour (35.1% vs 34.6%; P = .89), in survival until hospital discharge (11.4% vs 10.4%; P = .64), or in the median MMSE score of survivors (37 in both groups). For patients who collapsed outside the hospital, there were also no significant differences between the standard (n = 510) and ACD (n = 501) CPR groups in survival for 1 hour (16.5% vs 18.2%; P = .48), in survival to hospital discharge (3.7% vs 4.6%; P = .49), or in the median MMSE score of survivors (35 in both groups). Exploration of clinically important subgroups failed to identify any patients who appeared to benefit from ACD CPR. CONCLUSIONS: ACD CPR did not improve survival or neurologic outcomes in any group of patients with cardiac arrest.

Estimation of arterial PCO2 in the elderly.

Arterial PCO2 (PaCO2), determined directly in the radial artery, was compared with indirect estimates of PCO2 in six elderly men (mean age 73.8 yr). Estimates of PaCO2 included arterialized venous PCO2 (PavCO2); end-tidal PCO2; mean alveolar PCO2, calculated by using a reconstruction of the alveolar oscillation in PCO2 and accounting for the presence of dead space (time-weighted mean for PCO2 throughout the respiratory cycle); and values calculated by using the empirical formula developed by Jones et al. (N. L. Jones, D. G. Robertson, and J. W. Kane. J. Appl. Physiol. 47: 954-960, 1979), which incorporates end-tidal PCO2 and tidal volume (PaCO2 derived from end-tidal PCO2 and VT). Measurements were made at rest and during cycle ergometry at 25 and 50 W while the subjects breathed various gas mixtures (euoxic-eucapnic, hypoxic-eucapnic, hyperoxic-eucapnic, and hyperoxic-hypercapnic). The mean differences between the estimates and the actual PaCO2 at rest and in 25- and 50-W exercise were as follows: PavCO2, 0.3 +/- 0.7 (SD), -0.1 +/- 0.7, and 1.8 +/- 1.2 Torr; end-tidal PCO2, 2.9 +/- 1.7, 4.0 +/- 3.1, and 3.7 +/- 3.2 Torr; time-weighted mean of alveolar PCO2, 2.6 +/- 1.9, 3.3 +/- 3.1, and 3.6 +/- 3.8 Torr; and PaCO2 derived from end-tidal PCO2 and VT, 2.4 +/- 1.3, 1.3 +/- 3.0, and 0.6 +/- 2.9 Torr. It is concluded that mean PavCO2 agreed most closely with mean PaCO2 both at rest and in exercise. All methods of deriving PaCO2 using measurements from the respired gases overestimated arterial values at rest. Of the noninvasive techniques, mean estimates calculated using the regression equation developed by Jones et al. corresponded most closely with PaCO2 in exercise.