Cerebral haemodynamics during the Mueller manoeuvre in humans

Voluntary negative intra‐thoracic pressure (Mueller manoeuvre) is known to reduce arterial blood pressure (ABP). To investigate changes in cerebral blood flow velocity (CBFV) during 15 s Mueller manoeuvres at –30 mmHg intra‐thoracic pressure, 27 young (aged 21–31 years, group A) and 11 older (52–64 years, group B) healthy adults were studied using transcranial Doppler and non‐invasive ABP measurement (Finapres). After closely following the initial ABP drop, CBFV showed an overshoot during temporary recovery of ABP. Then ABP and CBFV decreased significantly to below baseline. While ABP declined further until the end of the manoeuvre, CBFV increased in group A 4·7 s (2·4–8·5) (median and range) and in group B 5·7 s (4·1–7·2) after the onset of the CBFV decrease. Critical closing pressure (CCP), calculated for each cardiac cycle from the dynamic pressure–flow relationship (DPFR), indicated a reduction of intra‐cranial pressure during the first half of the strain. DPFR‐related estimation of cerebrovascular resistance provided a more physiological response than the conventional cerebrovascular resistance quotient ABP/CBFV, and decreased about 1·5 s before the observed CBFV increase. A modification of the previously described dynamic auto‐regulation index ROR correlated significantly with CO₂ reactivity values (r=0·61, P=0·001). In conclusion, changes in CBFV during Mueller manoeuvres are likely to reflect dynamic cerebral auto‐regulation and may provide an estimate of dynamic cerebral auto‐regulation capacity. In older adults, the maximal dynamic auto‐regulatory response seems to be unchanged, but the onset of reaction is slightly delayed.     

Evaluation of impaired dynamic cerebral autoregulation by the Mueller manoeuvre

Arterial blood pressure (ABP) shows polyphasic changes during the Mueller manoeuvre (voluntary negative intrathoracic pressure). The aim of the present study was to investigate (1) whether these changes could be applied to detect impaired dynamic cerebral autoregulation (dCA) in carotid stenosis and (2) whether the degree of indicated impairment correlates with transfer function phase as another current measure for dCA (deep breathing method) and CO₂‐reactivity. We examined 13 patients with severe unilateral carotid artery stenosis and 16 age‐matched controls during 15‐s Mueller manoeuvres (MM) at ?30 mmHg using bilateral transcranial Doppler sonography and non‐invasive ABP recordings (Finapres, 2300, Ohmeda, Englewood, CO, USA). After an initial biphasic oscillation, cerebral blood flow velocity (CBFV) and ABP decreased to below baseline. CBFV reincreased in controls and on contralateral sides in patients 6·0 s (3·8–9·5 s, median and range) after the onset of the decrease, despite a further fall in ABP. CBFV over the affected side revealed a significantly delayed reincrease (8·0 (5·6–10·3) s; P<0·01) combined with a relatively flat and inertial amplitude behaviour. An applied autoregulation index derived from the MM (mROR), phase shift and CO₂‐reactivity were severely reduced on the affected side in patients (P<0·01). Reduction of the mROR correlated significantly with reduction of phase shift (r=0·69; P=0·002) and CO₂‐reactivity (r=0·78; P=0·002). In conclusion, the different cerebral haemodynamic pattern during the MM in patients is likely to reflect impaired dCA. The degree of indicated impairment correlates with that of transfer function phase and CO₂‐reactivity. Therefore, the MM represents a convenient method for grading of compromised cerebral haemodynamics in patients with carotid artery stenosis.     

Variability of automated carotid intima‐media thickness measurements by novice operators

Carotid intima‐media thickness (C‐IMT) measurements provide a non‐invasive assessment of subclinical atherosclerosis. The aim of the study was to assess the inter‐ and intra‐observer variability of automated C‐IMT measurements undertaken by two novice operators using the Panasonic CardioHealth Station. Participants were free from cardio‐metabolic disease, and each underwent serial bilateral C‐IMT ultrasound measurements. Immediate interoperator measurement variability was calculated by comparing initial measurements taken by two operators. Immediate retest variability was calculated from two consecutive measurements and longer term variability was assessed by conducting a further scan 1 week later. Fifty apparently healthy participants (n = 20 females), aged 26·2 ± 5·0 years, were recruited. Operator 1 recorded a median (interquartile range) right and left‐sided C‐IMT of 0·471 mm (0·072 mm) and 0·462 mm (0·047 mm). Female's right and left C‐IMT were 0·442 mm (0·049 mm) and 0·451 mm (0·063 mm), respectively. The limits of agreement (LoA) for immediate interoperator variability were ?0·063 to 0·056 mm (mean bias ?0·003 mm). Operator 1's immediate retest intra‐operator LoA were ?0·057 to 0·046 mm (mean bias was ?0·005 mm). One‐week LoA were ?0·057 to 0·050 mm (mean bias ?0·003 mm). Operator 2 recorded median right and left‐sided C‐IMT of 0·467 mm (0·089 mm) and 0·458 mm (0·046 mm) for males, respectively, whilst female measurements were 0·441 mm (0·052 mm) and 0·444 mm (0·054 mm), respectively. Operator 2's intra‐operator immediate retest LoA were ?0·056 to 0·056 (mean bias 相似文献   

Reliability of dynamic cerebral autoregulation measurement using spontaneous fluctuations in blood pressure

Spontaneous fluctuations in BP (blood pressure) and subsequent change in CBFV (cerebral blood flow velocity) in the MCA (middle cerebral artery) can be used to assess dynamic cerebral autoregulation using transfer function analysis; however, the reliability of this technique has not been assessed, in particular the contribution of intra-subject variability relative to inter-subject variability. Three bilateral CBFV, BP and RR interval recordings were performed in ten healthy volunteers on four separate occasions over a 2-week period. Data were analysed to provide the ARI (autoregulatory index), CBFV, RAP (resistance-area product) and CrCP (critical closing pressure). We also measured systolic and diastolic BP, and resting HR (heart rate). We calculated the SEM (standard error of measurement) and the ICC (intra-class correlation coefficient) and their 95% CIs (confidence intervals) for each parameter to assess their absolute (intra-subject) and relative (inter-subject) reliability. The CV (coefficient of variation) of SEM ranged from 1.7% (for CBFV) to 100.0% (for RAP), whereas the ICC was <0.5 for ARI, rising to >0.8 for CBFV and diastolic BP. These data demonstrate excellent absolute and relative reliability of CBFV, whereas ARI is of comparable reliability with the measurement of HR. Using these results it is possible to determine the sample size required to demonstrate a change in ARI, with a sample of 45 subjects in each group required to show a change in ARI of 1, whereas to detect a change in ARI >2 would require only 11 subjects per group. The results of the present study could be valuable to the future planning of cerebral autoregulation studies, but more work is needed to understand the determinants of intra-subject variability in autoregulatory parameters.     

Reproducibility of orthostatic changes in cerebral oxygenation in healthy subjects aged 70 years or older

In the elderly, standing can frequently be accompanied by blood pressure (BP) changes and cerebral symptoms such as dizziness, fall, or even syncope, but this may vary from day‐to‐day. Therefore, we aimed to investigate the reproducibility of orthostatic responses of cerebral cortical oxygenation and systemic haemodynamics in elderly subjects. In 27 healthy elderly subjects (age 70–84 years), changes in systolic BP (SBP), diastolic BP (DBP), heart rate (HR) and stroke volume (SV) were continuously monitored by Finapres (Finger Arterial Pressure), and changes in oxyhaemoglobin ([O₂Hb]) and deoxyhaemoglobin ([HHb]) concentrations were continuously measured over the right frontal cortex by near infrared spectroscopy (NIRS) during supine rest and 10 min of active standing on two separate occasions. SBP and DBP increased by 6·7 ± 15·4 mmHg (P<0·05, mean ± SD) and 8·2 ± 6·4 mmHg (P<0·01), respectively, whereas HR increased by 9·5 ± 5·0 bpm (P<0·01) and SV decreased by –8·3 ± 7·4 ml (P<0·01) during standing on the first occasion. [O₂Hb] decreased by –3·9 ± 2·9 μmol l^–1 (P<0·01), while [HHb] increased by 1·8 ± 2·2 μmol l^–1 (P<0·01). Group‐averaged orthostatic changes in cortical oxygenation and systemic haemodynamics were very similar on the two occasions, although an intraindividual variation was found. Cortical oxygenation changes were not accompanied by severe cerebral symptoms. Active standing induced reproducible group‐averaged frontal cortical oxygenation declines in healthy elderly subjects, although an intraindividual day‐to‐day variability was present, possibly related to the variability of orthostatic BP responses. These findings indicate that cerebral autoregulation fails to compensate completely for postural changes in elderly subjects, which might predispose elderly subjects to ischaemic cerebral symptoms.     

Computerized analysing system using the active contour in ultrasound measurement of carotid artery intima‐media thickness

Background and purpose B‐mode measurement of the carotid intima‐media (IM) thickness (T) based on manual tracing (MT) procedures are dependent on the subjectivity of the reader and the existing automatic tracing procedures often fail to detect the IM boundaries accurately. The purpose of this study was to compare the tracing results of the IM boundaries of the carotid wall with a new automatic identification (AI) procedure, based on an active contour model, and computer‐assisted manual tracing (MT). Methods The detection of the IM boundaries was performed with both procedures in 126 ultrasound images [63 each of the common carotid artery (CCA) and carotid bulb] along the far wall of the distal CCA and the carotid bulb. Intra‐ and inter‐reader variability for mean and maximum IMT with AI and MT and accuracy of identification of both IM boundaries were evaluated. Results Using MT the intra‐ and inter‐reader variability amounted to 0·01–0·03 and 0·03–0·07 mm, respectively. The variability was slightly higher in the carotid bulb than in the CCA. Using AI the variability was almost eliminated. Mean and maximum IMT were measured systematically lower by AI compared with MT in all regions by 0·01 mm. The accuracy of identification was similar for both IM boundaries, but lower in the carotid bulb region than in the CCA. Conclusions The new AI procedure identifies both IM boundaries in the region of the far wall of the CCA and carotid bulb with high precision, and eliminates most of the intra‐ and inter‐reader variability of the IMT measurement using MT.     

Tracer kinetics analysis of dynamic contrast‐enhanced CT and MR data in patients with squamous cell carcinoma of the upper aerodigestive tract: comparison of the results

Purpose: (i) To evaluate the feasibility of tracer kinetics analysis of dynamic contrast‐enhanced (DCE) CT and T2‐weighted MR data of squamous cell carcinoma (SCCA) of the upper aerodigestive tract. (ii) To compare functional parameters derived by both modalities and examine the interchangeability of them as well as the intra‐ and inter‐rater agreement. Materials and methods: Dynamic contrast‐enhanced‐CT and MR images of 23 patients with SCCA were postprocessed using a distributed‐parameter (DP) tracer kinetic model. The evaluated parameters included blood flow (F), intravascular blood volume (v₁), extravascular extracellular blood volume (v₂), intravascular mean transit time (t₁), lag time (t₀), permeability surface area product (PS) and extraction ratio (E). Mean perfusion values, based on region‐of‐interest analysis, of the tumors and the healthy muscle tissue were compared and correlated. Inter‐rater and intra‐rater variability were assessed. Interchangeability of the tumor functional parameters was tested using Pearson’s correlation coeficients and Bland–Altman plots. Results: The mean values in tumor and healthy muscle tissues were significantly different for each modality (0·0001≤P≤0·03). The mean values of all tumor perfusion parameters apart from v₂ and E were significantly different (0·001≤P≤0·009) between the two modalities. The intra‐rater variability was good to very good for all parameters. The inter‐rater variability was moderate to good. Bland–Altman plots of F, t₁, t₀, and v₂ showed moderate interchangeability. There was a proportionality error in v₁ and PS graphs. Conclusion: The estimation of functional parameters in SCCA is feasible using DCE‐CT and ‐MR with a DP model. The parameters are mostly significantly different and the interchangeability of them is limited.     

Cerebral perfusion information obtained by dynamic contrast‐enhanced phase‐shift magnetic resonance imaging: comparison with model‐free arterial spin labelling

Phase‐shift time curves following a bolus injection of gadolinium contrast agent were registered for grey‐matter regions and large vessels in 14 subjects. Deconvolving a tissue phase‐shift curve with a phase‐based arterial input function resulted in a tissue residue function R(t). The peak value of R(t) provided a relative cerebral blood flow (CBF) index, while the area‐to‐height ratio of R(t) provided quantitative mean transit time (MTT). For comparison, quantitative CBF values in grey matter were acquired using model‐free arterial spin labelling (ASL). The phase‐based relative CBF estimates showed good linear correlation with ASL‐based CBF (r = 0·82). Grey‐matter MTT was 4·9 ± 1·1 s (mean ± SD).     

Temporal age‐related changes in spectral,fractal and complexity characteristics of heart rate variability

Cross‐sectional studies have suggested that heart rate (HR) variability, analysed using traditional time and frequency domain methods, is related to ageing, but no longitudinal studies have estimated the age dependence of HR fluctuation. This study evaluated temporal age‐related changes in 12‐h measures of HR variability among 109 patients with coronary artery disease (CAD), who underwent repeat Holter recordings at 32‐month intervals. Time and frequency domain measures, along with fractal and complexity measures of HR variability, were determined at the baseline and after 32 months. Changes in HR dynamics were compared with various laboratory variables, exercise data and angiographic progression of CAD. Traditional time and frequency domain measures of HR variability did not change significantly during the follow‐up, but the power‐law scaling slope decreased from ?1·29 ± 0·20 to ?1·36 ± 0·23 (P<0·01) and the short‐term fractal exponent (α₁) of HR dynamics from 1·29 ± 0·14–1·22 ± 0·18 (P<0·001). The approximate entropy value also decreased from 1·00 ± 0·19 to 0·95 ± 0·18 (P<0·05). The changes in HR behaviour were not related to demographic data, laboratory values or angiographic progression of CAD. Only a weak correlation was observed between the change in the power‐law slope and the baseline glucose value (P<0·05). This longitudinal study shows that the fractal characteristics of HR dynamics and the complexity properties of R‐R intervals undergo rapid changes along with ageing, and that fractal and complexity analysis techniques are more sensitive than traditional analysis methods in documenting temporal age‐related changes in HR behaviour.     

Continuous estimates of dynamic cerebral autoregulation: influence of non-invasive arterial blood pressure measurements

Temporal variability of parameters which describe dynamic cerebral autoregulation (CA), usually quantified by the short-term relationship between arterial blood pressure (BP) and cerebral blood flow velocity (CBFV), could result from continuous adjustments in physiological regulatory mechanisms or could be the result of artefacts in methods of measurement, such as the use of non-invasive measurements of BP in the finger. In 27 subjects (61+/-11 years old) undergoing coronary artery angioplasty, BP was continuously recorded at rest with the Finapres device and in the ascending aorta (Millar catheter, BP(AO)), together with bilateral transcranial Doppler ultrasound in the middle cerebral artery, surface ECG and transcutaneous CO(2). Dynamic CA was expressed by the autoregulation index (ARI), ranging from 0 (absence of CA) to 9 (best CA). Time-varying, continuous estimates of ARI (ARI(t)) were obtained with an autoregressive moving-average (ARMA) model applied to a 60 s sliding data window. No significant differences were observed in the accuracy and precision of ARI(t) between estimates derived from the Finapres and BP(AO). Highly significant correlations were obtained between ARI(t) estimates from the right and left middle cerebral artery (MCA) (Finapres r=0.60+/-0.20; BP(AO) r=0.56+/-0.22) and also between the ARI(t) estimates from the Finapres and BP(AO) (right MCA r=0.70+/-0.22; left MCA r=0.74+/-0.22). Surrogate data showed that ARI(t) was highly sensitive to the presence of noise in the CBFV signal, with both the bias and dispersion of estimates increasing for lower values of ARI(t). This effect could explain the sudden drops of ARI(t) to zero as reported previously. Simulated sudden changes in ARI(t) can be detected by the Finapres, but the bias and variability of estimates also increase for lower values of ARI. In summary, the Finapres does not distort time-varying estimates of dynamic CA obtained with a sliding window combined with an ARMA model, but further research is needed to confirm these findings in healthy subjects and to assess the influence of different physiological manoeuvres.     

Well‐being and cerebral oxygen saturation during acute heart failure in humans

Cerebral symptoms and near‐infrared spectrophotometry‐determined cerebral oxygen saturation (ScO₂) were followed in patients treated for normotensive acute congestive heart failure. The reproducibility and normal range for ScO₂ were established from 39 resting subjects without cardio‐respiratory disease: the ScO₂ ranged from 55 to 78% with a coefficient of variation for triple determination of 6%. Patients rated cerebral symptoms on a scale with end‐points of 0 (best) and 10 (worst). In eight patients with acute heart failure, arterial oxygen tension increased during decongestive treatment, from 9·1 (4·9–10) to 10·4 kPa (7·3–17); median with range, as did arterial oxygen saturation, from 94 (48–97) to 97% (87–99) (P<0·02), whereas the mean arterial pressure, heart rate and arterial carbon dioxide tension remained unchanged. The cerebral symptom score improved from 8 (3–10) to 1 (1–9) and the ScO₂ increased from 34 (20–58) to 50% (19–91) (P<0·02). A ninth patient presented with a silent but massive myocardial infarction: she was cerebrally obtunded with a ScO₂ of 18% and soon died. In patients with normotensive acute heart failure and cerebral symptoms, cerebral oxygen saturation is low, and during successful treatment ScO₂ increases with the well‐being of the patient.     

Test–retest reliability of the IDEEA system in the quantification of step parameters during walking and stair climbing

The aim of this investigation was to evaluate the inter‐ and intra‐session reliability of spatio‐temporal gait variables collected during walking and stair climbing with the Intelligent Device for Energy Expenditure and physical Activity (IDEEA) accelerometer‐based system. Eighteen healthy subjects (10 men, 8 women) completed a standardized indoor circuit comprised of walking and stair climbing. Intra‐and inter‐session reliability was investigated for several pertinent spatio‐temporal gait variables using intraclass correlations [ICC (3,1)]. Intra‐session reliability during walking showed a high reliability of the IDEEA with ICCs ranging between 0·84 (number of steps) and 0·97 (single limb support/double limb support). The ICCs for stair climbing were slightly lower than those during walking with values ranging between 0·74 (step duration) and 0·92 (number of steps). Inter‐session reliability during walking showed a high reliability of the IDEEA between all trials, with values ranging between 0·87 (speed) to 0·98 (step duration). The ICCs of stair climbing were again lower than those during walking with values ranging from 0·64 (swing duration) to 0·79 (number of steps). The IDEEA accelerometer‐based system provided a highly reliable measurement of spatio‐temporal variables, in healthy subjects, during walking with moderately reduced correlations during stair climbing.     

Reliability of Vertical Jump Performance evaluated with contact mat in elderly women

The aim of this study was to evaluate the reliability of the vertical jump (VJ) using a contact mat in elderly women. Thirty‐one physically active women aged 69·5 ± 5·6 years participated in this study. Jump performance was evaluated with a contact mat. The first testing session (s1) consisted of four countermovement jumps interspersed with 40 s rest intervals. After a period of 5–7 days, volunteers performed the second session (s2) utilizing the same procedures. The intersession statistical analysis was calculated considering the two highest jumps, one obtained in each section. The intra‐session analysis utilized all eight jumps, all four from each section, and the differences between means were calculated by repeated measures ANOVA. Reliability was tested using the intra‐class correlation coefficient (ICC) and agreement by the Bland–Altman method. The intra‐ and inter‐subject variation percentage was calculated by the coefficient of variation (CV). Results: The intersession results displayed a high ICC (0·91; P<0·001) and a good agreement verified by the Bland–Altman method. There was a significant difference in the intra‐session analysis only in s2 between the jumps 2 and 4. Both in s1 and s2, the ICC was high (0·96; P<0·001; 0·95; P<0·001), and the within session reliability CV was low (10·14% and 9·07%). Conclusion: In physically active elderly women, VJ evaluation using a contact mat is a reliable method and could be used to estimate jump height. Additionally, the results of this study could serve as reference values in similar samples evaluated with the same procedures.     

Variability of time-domain indices of dynamic cerebral autoregulation

The intra- and inter-subject variabilities of the cerebral dynamic autoregulatory index (ARI) were studied in a group of 14 healthy subjects aged 23-51 years. An alternative index, derived from autoregressive-moving average (ARMA) modelling of the arterial blood pressure (ABP)-cerebral blood flow velocity (CBFV) dynamic relationship, named ARMA-ARI, is also proposed. The susceptibility of both indices to physiological sources of variability was studied by performing measurements during spontaneous respiration (SR), and controlled breathing at 6, 10 and 15 breaths min(-1). ABP was measured non-invasively (Finapres), CBFV was recorded with Doppler ultrasound in both middle cerebral arteries and end-tidal CO2 (EtCO2) was estimated with an infrared capnograph. ARI and ARMA-ARI were calculated as a summary measure for the whole of each recording period, and also continuously, using a 60 s moving data window. Respiration did not have an effect on either of these indices, despite significant, but relatively small, reductions in EtCO2 at 10 and 15 bpm, compared to SR. Very significant differences were observed between ARI and ARMA-ARI in relation to their stability, variability and sensitivity to discriminate between subjects. For continuous estimates the coefficient of variation of ARI was 30 +/- 21% compared to 15 +/- 8% for ARMA-ARI (p < 0.000). The cumulative probability distributions were also significantly different for the two indices for each of the respiratory manoeuvres. The greater stability and reduced variability of ARMA-ARI, in relation to the classic ARI, suggest that the former should be used in future studies of dynamic autoregulation, mainly in situations where an improved temporal resolution might be required, such as the investigation of vaso-vagal syncope or the physiology of exercise.     

Determination of the mitral papillary muscle positions by the septal‐to‐free wall arc ratio method

Background: Determination of mitral papillary muscle positions is of increasing interest in wide spectrum of clinical cardiology fields. Particularly, relative positioning of the papillary muscles between the inter‐ventricular septum and the left ventricular free wall is of interest. A reproducible method for determination of papillary muscle positions has not been established. In this study a new ‘septal‐to‐free wall arc ratio’ (SFAR) method for measuring papillary muscle positions is presented. The reproducibility of the SFAR method between echocardiographic (ECHO) and magnetic resonance (MRI) modalities and between observers is tested. Methods: Twenty subjects with structurally normal hearts in whom both MRI and ECHO were performed in 2007 were included in the study. Papillary muscle positions were determined using the SFAR method. Inter‐modality (ECHO and MRI) and inter‐observer reproducibility of the methods was assessed by calculating correlation coefficients and the mean difference from agreement. Results: The inter‐modality correlation of the SFAR method was 0·80 (P < 0·0001) for both papillary muscles. The mean difference of measurements from agreement was 4% for the superior and 2% for the inferior papillary muscle. The inter‐observer correlation was 0·93 (P < 0·0001) for superior and 0·90 (P = 0·0002) for inferior papillary muscle. The mean inter‐observer difference from agreement was 2% for superior and 3% for inferior papillary muscle. Conclusions: The SFAR method may be applied in wide range of both scientific and clinical medical fields as a reproducible method for determination of papillary muscle positions with the benefit of estimation of relative papillary muscle positions both from the septum and the free wall.     

Short-term variability of cerebral blood flow velocity responses to arterial blood pressure transients

The time course of mean beat-to-beat changes in cerebral blood flow velocity changes induced by spontaneous transients in mean arterial blood pressure was studied in a group of 39 healthy subjects, ages 40 +/- 15 (SD) years. Continuous 10-min noninvasive recordings of cerebral blood flow velocity (CBFV) from both middle cerebral arteries (MCA) with Doppler ultrasound (US) and simultaneous beat-to-beat arterial blood pressure (ABP) were made. A total of 522 spontaneous positive transients of ABP and CBFV were extracted with a maximum of 15 transients for each subject. The CBFV transient amplitude was normalized by the corresponding ABP change and the area-under-the-curve (AUC) of the falling phase was used to classify the CBFV regulatory response as either weak, moderate or strong. The coherent average of ABP and CBFV of each category confirmed the consistency of this classification, reinforced by the agreement of separate averages for recordings from the right and left MCA. All 39 subjects showed at least two categories of transients, with all three categories present in 33 subjects (right MCA) and 29 subjects (left MCA), respectively. These results indicate a significant short-term variability of CBFV responses in healthy subjects whose origin remains unexplained.     

A paracetamol‐pasta test for assessing gastric emptying in healthy and diabetic subjects

Previous studies have shown that the relationship between gastrointestinal symptoms and gastric emptying is weak. Therefore the quantitative assessment of gastric emptying with a relatively simple, non‐invasive test would be of considerable clinical value in insulin‐treated diabetic patients to identify those with disturbed gastric emptying. The aim of this investigation was to evaluate the inter‐ and intra‐subject variability of a paracetamol‐pasta test in healthy subjects and in IDDM patients. Eighteen healthy subjects (8 women) with a mean age of 37 years (range 19–68) and 19 IDDM patients (10 women) with a mean age of 48 years (range 25–62) and mean duration of diabetes of 28 years (range 6–52) were studied on two occasions with an interval of 1 to 4 weeks. After an overnight fast the subjects ingested a standardized pasta meal mixed with 2?g paracetamol in a period of 15?min. Blood samples were drawn at regular intervals after meal intake and analysed for paracetamol (P) and blood glucose. The serum levels of P were significantly lower at 15?min in diabetic patients. The intra‐subject coefficients of variation (CV%) of the areas under the serum paracetamol concentration‐time curve (AUC) were almost identical in healthy and diabetic subjects, while the intra‐subject CV of the P‐Tmax was considerably lower in diabetic patients as well as markedly lower than the corresponding inter‐subject CV. The inter‐subject CVs of all parameters calculated were generally higher in diabetic patients. This study indicates that the assessment of paracetamol absorption kinetics during a paracetamol‐pasta test is reproducible in healthy as well as in diabetic subjects. Diabetic patients with non‐optimal glucose control and without a case history indicating gastro‐duodenal motor function disturbances achieve lower serum concentration of P at 15?min and generally display a higher inter‐individual variability indicative of subclinical disturbances of gastric emptying in this group of patients.     

Anatomical vertebral artery hypoplasia and insufficiency impairs dynamic blood flow regulation

Recent studies have suggested that vertebral artery (VA) hypoplasia is a predisposing factor for posterior cerebral stroke. We examined whether anatomical vertebrobasilar ischemia, i.e., unilateral VA hypoplasia and insufficiency, impairs dynamic blood flow regulation. Twenty‐eight female subjects were divided into three groups by defined criteria: (i) unilateral VA hypoplasia (n = 8), (ii) VA insufficiency (n = 6), and (iii) control (n = 14). Hypoplastic VA criterion was VA blood flow of 40 ml min^?1, whereas VA insufficiency criterion was net (left + right) VA blood flow of 100 ml min^?1 or less. We evaluated left, right, and net VA blood flows by ultrasonography during hypercapnia, normocapnia, and hypocapnia to evaluate VA CO₂ reactivity. The unilateral VA hypoplasia group showed lower CO₂ reactivity at hypoplastic VA than at non‐hypoplastic VA (2·65 ± 0·58 versus 3·00 ± 0·48% per mmHg, P = 0·027) and net VA CO₂ reactivity was preserved (Unilateral VA hypoplasia, 2·95 ± 0·48 versus Control, 2·93 ± 0·42% per mmHg, P = 0·992). However, the VA insufficiency group showed a lower net VA CO₂ reactivity compared to the control (2·29 ± 0·55 versus 2·93 ± 0·42% per mmHg, P = 0·032) and the unilateral VA hypoplasia (P = 0·046). VA hypoplasia reduced CO₂ reactivity, although non‐hypoplastic VA may compensate this regulatory limitation. In subjects with VA insufficiency, lowered CO₂ reactivity at the both VA could not preserve normal net VA CO₂ reactivity. These findings provide a possible physiological mechanism for the increased risk of posterior cerebral stroke in subjects with VA hypoplasia and insufficiency.     

Ultrasound measurements of carotid intima–media thickness by two semi‐automated analysis systems

Increased carotid intima–media thickness (cIMT) is associated with an increased risk of cardiac events and stroke. Several semi‐automated edge‐detection techniques for measuring cIMT are used for research and in clinical practice. Our aim was to compare two currently available semi‐automated techniques for the measurement of cIMT. Carotid ultrasound recordings were obtained from 99 subjects (mean age 54·4 ± 8·9 years, range 33–69) without known cardiovascular diseases using a General Electric (GE) Vivid 7 ultrasound scanner, 8‐MHz transducer. The far‐wall cIMT was evaluated 1–2 cm proximal to the carotid bulb. Three diastolic images (ECG R‐wave) from the left and three images from the right common carotid arteries were analysed using GE and Artery Measurement System (AMS) semi‐automated softwares. Mean systolic and diastolic blood pressures were 120 ± 13 and 76 ± 8 mmHg, respectively. The cIMT_mean (left + right)/2 by GE and cIMT_mean (left + right)/2 AMS were highly correlated (r = 0·92, P<0·001). Higher values were measured by GE (0·72 ± 0·12 mm) compared with AMS (0·69 ± 0·12 mm), and this was significant (P<0·001). The coefficients of variation for the intra‐observer variability of cIMT_mean (left + right)/2 were 1·0% (GE) and 2·2% (AMS). cIMT_mean measured by GE's semi‐automated edge‐detection method correlated well with that measured by AMS. However, there were small but significant systematic differences between the cIMT_mean values measured by the two techniques. Thus, the use of only one type of measurement program seems favourable in follow‐up studies and when evaluating treatment effects.     

Reproducibility and variability of digital thermal monitoring of vascular reactivity

Background: Previous studies demonstrated that digital thermal monitoring (DTM) of vascular reactivity, a new test for vascular function assessment, is well correlated with Framingham Risk Score, coronary calcium score and CT angiography. This study evaluates the variability and reproducibility of DTM measurements. We hypothesized that DTM is reproducible, and its variability falls within the accepted range of clinical diagnostic tests. Method: A fully automated DTM device (VENDYS, Endothelix Inc., Houston, TX, USA) was used for repeated measurement of vascular function in 18 healthy volunteers (age 35 ± 4 years, 74% men) after 24 h. All subjects underwent overnight fasting, and the test was preceded by 30‐min rest in a supine position inside a dimmed room with temperature 22–24°C. The measurements were obtained during and after a 2‐min supra systolic arm‐cuff occlusion–induced reactive hyperaemia procedure. As a part of this study, the Doppler ultrasound hyperaemic, low‐frequency, blood velocity of radial artery and a fingertip DTM of vascular function were compared simultaneously. Postcuff deflation temperature rebound and area under the curve, DTM indices of vascular function, were studied. Results: Temperature rebound area under the curve correlated closely with Doppler hyperaemic, low‐frequency, blood velocity (r = 0·97, P = 0·0001). Day‐to‐day intra‐subject variability was 6·2% for baseline temperature, 8·7% for mean blood pressure and 11·4% for heart rate. The coefficient of repeatability of temperature rebound and area under the curve were 2·4% and 2·8%. Conclusion: In a controlled environment, the repeatability of DTM is excellent. DTM can be used as a reproducible and operator‐independent test for non‐invasive measurement of vascular function.