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Biomedical subjects

Carlo Franzini

Publications and source records attributed to Carlo Franzini.

At least 19 recordsLinked to original sources
PubMed2006

Trueness verification and traceability assessment of results from commercial systems for measurement of six enzyme activities in serum: an international study in the EC4 framework of the Calibration 2000 project.

BACKGROUND: The in vitro diagnostics directive of the European Union requires traceability to higher order reference measurement procedures and materials for analytes in assuring the result trueness and comparability of laboratory measurements. Manufacturers must ensure that the systems they market are calibrated against available reference systems. Validation of metrologically traceable calibrations is, however, required. METHODS: A commutable serum-based material was analyzed in three reference laboratories and target values for six enzymes (ALT, AST, CK, GGT, LD, amylase) were assigned using IFCC reference measurement procedures. 70 laboratories in Germany, Italy, and The Netherlands measured the same enzymes in the material using procedures from six commercial companies. A system for maximum allowable error was developed from the biological variation model and the results of the various procedures were tested on their compliance to trueness and between-laboratory and within-laboratory variations relative to the maximum allowable. RESULTS: For ALT results were relatively good. >95% of laboratories using systems from Dade, Olympus, Ortho and Roche are expected to comply traceability within the biologically derived limits, and 94% respectively 89% from Abbott and Beckman. For AST and GGT only Dade respectively Olympus fully complied. For CK all companies showed significant bias. Nevertheless >95% of laboratories applying Abbott, Beckman and Roche systems will comply. Finally, LD and amylase measurements require significant improvement. Some manufacturers continue to sell on the European market assays giving results which are not traceable to the internationally accepted reference systems. CONCLUSIONS: The traceability of enzyme measurements obtained with routine procedures to internationally accepted IFCC reference systems is not yet satisfactorily accomplished in clinical practice.

Biomedical Research↗
PubMed2006

Sleep-dependent changes in cerebral oxygen consumption in newborn lambs.

During rapid-eye-movement (REM) sleep in adult subjects, the cerebral metabolic rate of oxygen consumption (CMRO(2)) is as high as that during wakefulness. We investigated whether CMRO(2) during active sleep is already at the waking level in newborn life, to support the role of active sleep as a state of endogenous brain activation during early postnatal development. Newborn lambs, 2-5 days old (n = 6), were instrumented with electrodes for sleep-state scoring, catheters for blood sample withdrawal and pressure monitoring, and a transit-time ultrasonic blood-flow probe around the superior sagittal sinus. At the age of 19 +/- 3 days, blood samples were obtained simultaneously from the carotid artery and the superior sagittal sinus during uninterrupted epochs of wakefulness, quiet sleep, and active sleep. The arteriovenous difference in blood oxygen concentration was multiplied by cerebral blood flow to determine CMRO(2). CMRO(2) during active sleep (47 +/- 5 micromol min(-1)) was similar to the value in wakefulness (44 +/- 6 micromol min(-1)) and significantly higher than in quiet sleep (39 +/- 5 micromol min(-1), P < 0.05). These data show that active sleep provides newborn lambs with brain activity at a level similar to that in wakefulness in terms of cerebral oxygen metabolism. The high CMRO(2) during active sleep supports its functional role during early postnatal development, when time spent in active sleep is at a lifetime maximum, albeit constituting a metabolic challenge for newborns, because of the impairment of systemic and cerebral vascular regulation in this sleep state.

Animals↗
PubMed2005

The REALAB project: a new method for the formulation of reference intervals based on current data.

BACKGROUND: In a primary healthcare center concerned more with maintaining wellness than with diagnosing and monitoring illness, it is particularly important to compare patients' results with reference intervals derived from a matched population by use of defined statistical methods. METHODS: Laboratory results over a 3-year period (approximately 15,000,000 records; 197,350 individuals) were retrieved from our laboratory information system. An inclusion/exclusion procedure for individual patients was applied based on (a) presence of at least 1 of 23 previously defined "basic tests"; (b) only 1 measurement per test by the laboratory over the 3-year period; (c) for each test, absence of any abnormality in the correlated tests. Before the third step, correlations among quantities were assessed by a Spearman correlation matrix, comparing each of the 23 basic tests with all remaining tests by use of a novel multivariate algorithm. RESULTS: The initial sample group (n = 197,350) was reduced stepwise by the selection criteria outlined above to 166,027, then to 93,649, and finally to 61 246 individuals constituting our reference sample group. Results from the last 2 groups were used to calculate sex-specific, and in some cases age-related, reference limits for the 23 basic tests and for 13 additional quantities. Reference limits were calculated throughout this study by nonparametric estimation of percentiles. CONCLUSION: Reference values derived by retrospective analysis of large samples of data obtained at a given institution are particularly suitable for the evaluation of results for the presenting patient population at that institution.

Adolescent↗
PubMed2005

Autoregulation of the cerebral circulation during sleep in newborn lambs.

Autoregulation is a vital protective mechanism that maintains stable cerebral blood flow as cerebral perfusion pressure changes. We contrasted cerebral autoregulation across sleep-wake states, as little is known about its effectiveness during sleep. Newborn lambs (n= 9) were instrumented to measure cerebral blood flow (flow probe on the superior sagittal sinus) and cerebral perfusion pressure, then studied during active sleep (AS), quiet sleep (QS) and quiet wakefulness (QW). We generated cerebral autoregulation curves by inflating an occluder cuff around the brachiocephalic artery thereby lowering cerebral perfusion pressure. Baseline cerebral blood flow was higher (P < 0.05) and cerebral vascular resistance lower (P < 0.05) in AS than in QW (76 +/- 8% and 133 +/- 15%, respectively, of the AS value, mean +/-s.d.) and in QS (66 +/- 11% and 158 +/- 30%). The autoregulation curve in AS differed from that in QS and QW in three key respects: firstly, the plateau was elevated relative to QS and QW (P < 0.05); secondly, the lower limit of the curve (breakpoint) was higher (P < 0.05) in AS (50 mmHg) than QS (45 mmHg); and thirdly, the slope of the descending limb below the breakpoint was greater (P < 0.05) in AS than QS (56% of AS) or QW (56% of AS). Although autoregulation functions in AS, the higher breakpoint and greater slope of the descending limb may place the brain at risk for vascular compromise should hypotension occur.

Animals↗
PubMed2005

Sleep-related brain activation does not increase the permeability of the blood-brain barrier to glucose.

We compared blood-brain barrier (BBB) permeability to glucose between quiet wakefulness and rapid-eye-movement (REM) sleep to assess whether changes in BBB permeability play a role in coupling glucose supply to the physiologic metabolic needs of the brain. Male Sprague-Dawley rats were prepared with electrodes for wake-sleep state scoring and with arterial and venous catheters. Using the single-pass, dual-label indicator method, unidirectional glucose extraction by the brain and cerebral blood flow (CBF) were simultaneously measured during states of quiet wakefulness (n=12) or REM sleep (n=7). The product of BBB surface area and permeability to glucose (PS product) was computed in each state. During REM sleep, CBF significantly exceeded that during quiet wakefulness in all regions but the cerebellum, whereas the difference in the PS product between quiet wakefulness and REM sleep was not statistically significant in any brain region. In the brain as a whole, CBF significantly increased 29% from quiet wakefulness to REM sleep, while a nonsignificant 0.8% increase occurred in the PS product. During REM sleep, the increase in CBF indicates a higher rate of brain glucose consumption than in quiet wakefulness, given the tight flow-metabolism coupling in the brain. Therefore, these data show that modulation of BBB permeability to glucose is not a mechanism that provides 'energy on demand' during the physiologic brain activation characterising REM sleep.

Algorithms↗
PubMed2005

Sympathetic nervous control of the cerebral circulation in sleep.

Cerebral vessels are extensively innervated by sympathetic nerves arising from superior cervical ganglia, and these nerves might play a protective role during the large arterial pressure surges of active sleep (AS). We studied lambs (n=10) undergoing spontaneous sleep-wake cycles before and after bilateral removal of the superior cervical ganglia (SCGx, n=5) or sham ganglionectomy (n=5). Lambs were instrumented to record cerebral blood flow (CBF, flow probe on the superior sagittal sinus), carotid arterial pressure (P(ca)), intra-cranial pressure (P(ic)), cerebral perfusion pressure (Pcp=Pca-Pic) and cerebral vascular resistance (CVR). Prior to SCGx, CBF (mL min-1) was significantly higher in AS than in Quiet Sleep (QS) and Quiet Wakefulness (QW) (17+/-2, 13+/-3, and 14+/-3 respectively, mean+/-SD, P<0.05). Following SCGx, baseline CBF increased by 34, 31, and 29% respectively (P<0.05). CVR also decreased in all states by approximately 25% (P<0.05). During phasic AS, surges of Pca were associated with transient increases in Pcp, Pic and CBF. Following SCGx, peak CBF and Pic during surges became higher and more prolonged (P<0.05). Our study is the first to reveal that tonic sympathetic nerve activity (SNA) constricts the cerebral circulation and restrains baseline CBF in sleep. SNA is further incremented during arterial pressure surges of AS, limiting rises in CBF and Pic, possibly by opposing vascular distension as well as by constricting resistance vessels. Thus, SNA may protect cerebral microvessels from excessive distension during AS, when large arterial blood pressure surges are common.

Animals↗
PubMed2004

Sleep-dependent changes in the coupling between heart period and arterial pressure in newborn lambs.

This study assessed whether sleep-dependent changes in the relationship between heart period (HP) and mean arterial pressure (MAP) occur in newborn life. Electrodes for electrocorticographic, electromyographic, and electrooculographic monitoring and an arterial catheter for blood pressure recordings were implanted in 11 newborn lambs. HP and MAP beat-to-beat values were computed from 120-s blood pressure recordings during quiet wakefulness, active sleep, and quiet sleep. For each recording, the time shift at which the maximum of the HP versus MAP cross-correlation function was attained was identified. For each lamb and wake-sleep state, an average correlation coefficient was then computed corresponding to the median value of such time shifts. The maximum of the cross-correlation function was attained with HP lagging behind MAP. The corresponding mean correlation coefficient was significantly higher in quiet sleep (0.51 +/- 0.05) than either in quiet wakefulness (0.31 +/- 0.05) or in active sleep (0.29 +/- 0.03). Sleep-related differences in the correlation between HP and MAP were maintained after HP and MAP data were low-pass filtered at 0.3 Hz to remove their fast ventilatory oscillations. In conclusion, data indicate that the relationship between spontaneous fluctuations in HP and those in MAP is sleep-state dependent in newborn lambs. A positive HP versus MAP correlation with HP lagging behind MAP is consistent with baroreflex control of HP. Heart rhythm thus may be more tightly controlled by the baroreceptor reflex and less dependent on central autonomic commands in quiet sleep than either in quiet wakefulness or in active sleep.

Animals↗
PubMed2004

Sleep-related changes in the regulation of cerebral blood flow in newborn lambs.

STUDY OBJECTIVES: The interplay between cerebral perfusion pressure (CPP) and vascular resistance leads to fluctuations in cerebral blood flow (CBF). The relationship between fluctuations in CBF and those in CPP provides insight into the impact of the regulation of vascular resistance on CBF. The aim of this work was to study sleep-related changes in CBF regulation in newborn lambs, by quantifying the extent to which variability in CBF is related to that of CPP in the different wake-sleep states. DESIGN: Repeated-measurement within-subject. PARTICIPANTS: 8 newborn lambs. INTERVENTIONS: Chronic instrumentation with electrodes (electrocorticogram, electrooculogram, nuchal electromyogram), an arterial catheter (arterial pressure), a subdural catheter (intracranial pressure), and an ultrasonic flow probe around the superior sagittal sinus (CBF). MEASUREMENTS AND RESULTS: The CPP (difference between arterial and intracranial pressure) and CBF data sequences during quiet wakefulness, rapid-eye-movement (REM) sleep and non-REM sleep were subject to spectral analysis. The fraction of CBF variability explained by CPP variability (CPP vs CBF squared coherence in the range 0.05-0.3 Hz) was highest in REM sleep (0.653) and lowest in non-REM sleep (0.413). The CBF variability (coefficient of variation due to fluctuations in the range 0.05-0.3 Hz) was higher than CPP variability in all states, albeit not significantly in REM sleep. CONCLUSIONS: Results suggest that synchronized vasomotor fluctuations accounting for a quota of CBF variability not explained by CPP variability occur in all states in newborn lambs. Their relative contribution to CBF variability differs among wake-sleep states, being highest during non-REM sleep and lowest during REM sleep.

Animals↗
PubMed2004

High-density lipoproteins contribute to the alpha-1-globulin zone in capillary electrophoresis of human serum proteins.

Alpha-1-antitrypsin (AAT) and alpha-1-acid glycoprotein (AAG) are reported to be the main proteins contributing to the alpha-1-globulin capillary zone electrophoresis (CZE) zone, but the sum (AAT + AAG) showed lower than the alpha-1-globulin. We investigated the role of high-density lipoprotein (HDL), an additional protein migrating in the alpha-1-globulin zone, as a possible cause for such a gap. In a set of 98 sera we measured the alpha-1-globulin with a dedicated clinical capillary electrophoresis system, and AAT, AAG and apolipoprotein A-1 (ApoA) by immunonephelometry. The alpha-1-globulin were consistently higher than the sum (AAT + AAG), by (mean value +/- standard deviation) 1.70 +/- 0.88 g/L in 49 sera with low ApoA, and by 3.59 +/- 0.75 g/L in 49 sera with high ApoA. Corresponding figures in the comparison alpha-1-globulin/(AAT + AAG + ApoA) were reduced to 1.08 +/- 0.77 g/L and 1.67 +/- 0.70 g/L. It is concluded that HDL significantly contribute to the CZE alpha-1-globulin zone, but do not completely explain the differences between the electrophoretic and the immunochemical measurements. However, CZE alpha-1-globulin measurements give information about increases of the two major acute phase proteins comparable to specific protein measurements.

Alpha-Globulins↗
PubMed2004

Measurement of C-reactive protein: two high sensitivity methods compared.

C-reactive protein (CRP) is an acute phase marker and a predictor of the risk of developing atherosclerotic complications. However, as a predictor of this risk, high sensitivity measurements are needed, and high sensitive CRP (hsCRP) assays have been developed. In this study, we experimentally compared two hsCRP assays, based on nephelometry and turbidimetry, both implemented on automated analyzers. Linearity, imprecision, turbidity interference, and results in the assay of 96 samples have been compared. Method comparison of the same two analytical systems in the assay of CRP was also performed on the basis of results in an interlaboratory external quality assessment scheme (EQAS). The two systems were found to perform substantially equally, both in hsCRP and in CRP measurement, but in the hsCRP assay the precision of nephelometry (CV% in the interval 3.0-5.8) was lower than that of turbidimetry (CV% in the interval 1.8-2.3). The classification of results by the two methods into three predefined relative risk classes gave 18% rate of discordance, in any case by one class only. The two methods proved reliable and comparable in the measurement of hsCRP, but precision should be improved.

Arteriosclerosis↗
PubMed2004

Analytical variation in the measurement of serum monoclonal component by capillary electrophoresis.

The amount of serum monoclonal components (MC), and moreover, their variation with time are important factors for differentiating malignancy-associated from benign gammopathies. Capillary electrophoresis (CE) of serum proteins allows better quantitative measurement in comparison to conventional gel-supported electrophoresis. We investigated the analytical variation of CE measurement of serum MC of different sizes: the variation due to integration settings and the analytical variation of the CE procedure were assessed in separate experiments. "Small" MC (in the interval 4-14% of total protein) were measured with analytical imprecision (CV%) in the interval 5-25%. The step of setting the integration limits was found to generate an important portion of such an overall variability. The imprecision was negatively, nonlinearly related to MC concentration: at the "critical" MC value of 40% of total protein, the analytical imprecision was CV approximately 2.5%. The variation computed from sets of subsequent routine MC measurements in "stable" patients with MGUS, over observation intervals from 10 to 30 months, behaved similarly to the "pure" analytical variation measured experimentally. This suggested very low, if any, biological variation of MC. Differences between subsequent MC measurements in a patient should be interpreted in light of the analytical variation.

Antibodies, Monoclonal↗
PubMed2004

Plasma or serum samples: measurements of cardiac troponin T and of other analytes compared.

Conflicting data in the literature concern possible differences in the immunochemical measurement of cardiac troponins, either in plasma or in serum. In order to address this specific point, 96 serum and heparin-plasma pairs were obtained for cardiac marker measurement [cardiac troponin T (cTnT); myoglobin (Myo) and creatine kinase-MB isoenzyme (CK-MB)]; 29 additional "common" analytes were measured in 77 such samples. The cardiac markers were measured by electrochemiluminescence (Elecsys 2010, Roche); the other analytes by established automated methods (Modular, Roche). Mean plasma/serum ratios for cTnT (0.95), creatine kinase-MB (1.01) and myoglobin (0.99) were comparable with those of the 29 common analytes (interval of means 0.83-1.05). The distribution of the plasma-serum differences also showed similarities between cardiac markers and other analytes. A few outlier plasma-serum differences (3-5%) were measured for both categories of analytes. Addition of heparin to serum (51 samples) caused decreased cTnT (mean ratio 0.92). In 3 of 51 such samples the cTnT decrease was more marked, but in a second sample from the same subjects (1 week later) such a prominent, heparin-induced loss of cTnT no longer appeared. In conclusion, plasma-serum differences in immuno-reactive cTnT compare with those observed for other analytes. In occasional heparin-plasma samples immunochemical measurement of cTnT may give exceptionally low values. However, in our sample group of 96 patients (cTnT lower or higher than the cut-off in, respectively, 24 and 72 patients), no misclassification occurred if plasma instead of serum cTnT values were considered.

Biomarkers↗
PubMed2003

Brain capillary perfusion in the spontaneously hypertensive rat during the wake-sleep cycle.

Hypertension is accompanied by circulatory changes in the brain and in other vascular districts; at disease onset, these changes may be largely functional and dependent on metabolic and vegetative drives. The wake-sleep cycle is a major physiological source of ultradian variability in autonomic function and in cerebral blood flow and metabolism. Aim of the study was to investigate whether sleep induces functional changes in the brain microcirculation in the developing hypertensive state. The fraction of brain capillaries perfused by plasma (perfused/anatomical capillaries) was assessed in young (8-10 weeks) spontaneously hypertensive rats (SHR) during quiet wakefulness, quiet sleep and active sleep. The density of anatomical capillaries was assessed in two groups of animals using both a histochemical method (alkaline phosphatase, AP, for morphometric measurements) and an immunofluorescence method (anti-fibronectin antibodies, FN, to detect all existing capillaries). The density of perfused capillaries was determined by intravascular injection of a fluorescent marker. The fraction of anatomical capillaries perfused by plasma was always close to maximal (0.96-0.97), without significant variations among the states of the wake-sleep cycle, and was the same for AP-stained and FN-stained sections. Data thus indicate that in this model of essential hypertension no functional changes in plasma perfusion of cerebral capillaries occur in the early stages of the disease.

Alkaline Phosphatase↗