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Biomedical subjects

C Chiarla

Publications and source records attributed to C Chiarla.

At least 19 recordsLinked to original sources
PubMed2006

The relationship between albumin, other plasma proteins and variables, and age in the acute phase response after liver resection in man.

A large series of plasma albumin (ALB, g/dl) and simultaneous blood and clinical measurements were prospectively performed on 92 liver resection patients, and processed to assess the correlations between ALB, other plasma proteins, additional variables and clinical events. The measurements were performed preoperatively and at postoperative day 1, 3 and 7 in all patients, and subsequently only in those who developed complications or died. In patients who recovered normally ALB was 4.3 +/- 0.4 g/dl (mean +/- SD) preoperatively, 3.7 +/- 0.7 at day 1 and 3, and 3.9 +/- 0.4 at day 7. In patients with complications its decrease was more prolonged. In non-survivors it was 3.4 +/- 0.4 preoperatively, 3.0 +/- 0.4 at day 1, and then decreased further. Regression analysis showed direct correlations between ALB and pseudo-cholinesterase (CHE, U/l, nv 5300-13000), cholesterol (CHOL, mg/dl), iron binding capacity (IBC, mg/dl), prothrombin activity (PA, % of standard reference) and fibrinogen, an inverse correlation with blood urea nitrogen (BUN, mg/dl) for any given creatinine level (CREAT, mg/dl), and weaker direct correlations with hematocrit, other variables and dose of exogenous albumin. An inverse relationship found between ALB and age (AGE, years) became postoperatively (POSTOP) also a function of outcome, showing larger age-related decreases in ALB associated with complications (COMPL: sepsis, liver insufficiency) or death (DEATH). Main overall correlations: CHE = 287.4(2.014)(ALB), r = 0.73; CHOL = 16.5(1.610)(ALB) (1.001)(ALKPH), r = 0.71; IBC = 68.6(1.391)(ALB), r = 0.64; PA = 13.8 + 16.0(ALB), r = 0.51; BUN = 21.3 + 20.2(CREAT) - 6.2(ALB), r = 0.91; ALB = 5.0-0.013(AGE) - {0.5 + 0.003(AGE)( COMPL ) + 0.012(AGE)( DEATH )}( POSTOP ), r = 0.74 [p < 0.001 for each regression and each coefficient; ALKPH = alkaline phosphatase, U/l, nv 98-279, independent determinant of CHOL; discontinuous variables in italics label the change in regression slope or intercept associated with the corresponding condition]. These results suggest that altered albumin synthesis (or altered synthesis unable to compensate for albumin loss, catabolism or redistribution) is an important determinant of hypoalbuminemia after hepatectomy. The correlations with age and postoperative outcome support the concept that hypoalbuminemia is a marker of pathophysiologic frailty associated with increasing age, and amplified by the challenges of postoperative illness.

Acute-Phase Reaction↗
PubMed2005

Plasma arginine correlations in trauma and sepsis.

Arginine (ARG) is an amino acid (AA) with unique properties and with a key-role in the metabolic, immune and reparative response to trauma and sepsis. This study has been performed to characterize the correlations between plasma levels of ARG, of other AA and of multiple metabolic variables in trauma and sepsis. Two-hundred and sixty-three plasma amino-acidograms with a large series of additional biochemical and blood variables were obtained consecutively in 9 trauma patients who developed sepsis, undergoing total parenteral nutrition with dextrose, fat and a mixed AA solution containing 10.4% arginine. ARG was low soon after trauma, then it increased with increasing distance from trauma and with the development of sepsis. ARG was also directly related to the AA infusion rate (AAIR) and for any given AAIR, was lower after trauma than after the development of sepsis. ARG was also related directly to the plasma levels of most of the other AA, the best correlation being that with lysine (r(2) = 0.81, p < 0.001). These correlations were often shifted downwards (showing lower ARG for any given level of the other AA) in measurements performed after trauma, compared to those performed after development of sepsis; this effect was more pronounced for the correlations with branched chain AA. Correlations between ARG and non-AA variables were not particularly relevant. The best simultaneous correlates of ARG, among variables involved in plasma ARG availability, were citrulline level, AAIR and urinary 3-methylhistidine excretion (accounting for the effect of endogenous proteolysis) (multiple r(2) = 0.70, p < 0.001). Plasma ornithine (ORN), the AA more specifically linked to ARG metabolism, correlated with AAIR better than ARG and, for any given AAIR, was lower after trauma than after the development of sepsis. Correlations of ORN with other AA levels were poorer than those found for ARG, however ORN was directly related to white blood cell and platelet count, fibrinogen, transferrin, cholesterol and many AA clearances. These data show that changes in ARG in trauma and sepsis are correlated with changes in other AA and, within these correlations, reconfirm a tendency to lower ARG in trauma compared to sepsis. The strong correlation with lysine warrants a deeper assessment of the practical implications of interdependency between these two AA. The data also suggest that changes in plasma ORN in trauma and sepsis may reflect adequacy of AA substrate to support acute-phase and other synthetic processes.

Adolescent↗
PubMed2004

The relationship between plasma cholesterol, amino acids and acute phase proteins in sepsis.

The purpose of the study was to correlate degree of hypocholesterolemia to changes in plasma levels of amino acids and other metabolic variables in severely injured septic patients. Measurements included plasma cholesterol, full amino-acidograms, acute phase proteins, complementary variables and blood cell counts. The Fischer plasma molar amino acid ratio (leucine+isoleucine+valine)/(phenylalanine+tyrosine) was calculated. Plasma cholesterol for all measurements (n=145) was 3.1+/-1.1 mmol/L and, upon entry in the study, it was correlated inversely with sepsis severity score (p<0.05). Along the clinical course, changes in cholesterol were clearly paralleled by opposite changes in C-reactive protein, which was the best correlate of cholesterol (r2=0.70, p<0.0001). Furthermore cholesterol was inversely related to phenylalanine, fibrinogen, lactate and white blood cell count, and directly to the Fischer molar amino acid ratio, cystathionine, methionine, glycine and transferrin (r2 between 0.36 and 0.15, p<0.0001 for all). Within this pattern of correlations, cholesterol was also directly related to alkaline phosphatase, which accounted for the effect of cholestasis, when present. For any given value of the other variables, cholesterol increased significantly with increase in alkaline phosphatase (p<0.0001). C-reactive protein (CRP, mg/dl) and alkaline phosphatase (ALKPH, U/L) together in the same regression explained 79% of the variability of cholesterol (CHOL, mmol/L): CHOL=5.90-0.74[Log(e)CRP]+0.004[ALKPH]; multiple r2=0.79, p<0.0001. Inclusion in this regression of other variables did not increase the r2. By using only amino acid variables, the best fit was provided by a regression including the Fischer ratio and cystathionine, which explained 55% of the variability of cholesterol (multiple r2=0.55 p<0.0001), and this result was not improved by the inclusion of other amino acids. These data show that severity of hypocholesterolemia in sepsis is quantifiably related to changes in plasma amino acids, and to severity of acute phase response and metabolic decompensation. More study is needed to understand whether hypocholesterolemia in sepsis has only diagnostic or prognostic implications, or that it may also contribute actively to worsening of the disease.

Acute-Phase Proteins↗
PubMed2003

Co-variation of plasma sodium, taurine and other amino acid levels in critical illness.

This study investigates the relationship between changes in plasma sodium and changes in amino acid levels in a patient with post-traumatic sepsis and prolonged critical illness. Ninety-two consecutive measurements were performed at regular intervals over a period of many weeks; these consisted in the determination of full amino-acidograms, plasma sodium and complementary variables. A unique, highly significant inverse correlation between taurine and plasma sodium was found (r(2) = 0.48, p < 0.001). All other amino acids were unrelated, or much more weakly related, to sodium. Taurine was also strongly and directly related to phosphoethanolamine, glutamate and aspartate. Changes in sodium and in levels of these amino acids explained up to 86% of the variability of taurine. Besides, levels of these amino acids maintained a high degree of co-variation, remaining reciprocally related one to each other, directly, with r(2) ranging between 0.33 and 0.59 (p < 0.001 for all). There were similar findings for beta-alanine, which however was measured inconsistently. These data provide gross clinical evidence of a specific link binding plasma sodium and taurine levels, and may be consistent with occurrence of opposite and interdependent shifts of sodium and taurine between intravascular and extravascular space, to maintain osmoregulation. Co-variation of taurine with the other amino acids may be related to the same phenomenon, and/or to similarities in transport systems and chemical structure, or true metabolic interactions.

Aspartic Acid↗
PubMed2000

Taurine and pulmonary hemodynamics in sepsis.

This study has been performed to characterize the relationship between changes in plasma taurine (TAU) and hemodynamic patterns in sepsis. Analysis of 249 plasma aminoacidograms (AA-grams) and associated measurements in a group of critically ill, mechanically ventilated septic patients, showed that decreases in TAU were significantly correlated with increases in pulmonary artery pressure and pulmonary vascular resistance, and with worsening of pulmonary dysfunction. All cases requiring positive end-expiratory pressure greater than 10cmH2O had TAU lower than 50 microM/L. Low TAU was paralleled by decreases in other sulfur-containing AA, phosphoethanolamine, beta-alanine, glutamate and aspartate, within a pattern of greater metabolic dysregulation. These data provide evidence of a link between severity of pulmonary dysfunction and reduced TAU availability in clinical sepsis. The implications relate also to the need for specific investigations of the clinical effect of exogenous TAU on proinflammatory mediator-induced pulmonary dysfunction.

Adolescent↗
PubMed2000

The relationship between plasma taurine and other amino acid levels in human sepsis.

Although reports of decreased plasma taurine in trauma, sepsis and critical illness are available, very little is known about the relationships among changes in plasma taurine, other amino acid levels and metabolic variables. We analyzed a large series of plasma amino acid profiles obtained in trauma patients with sepsis who were undergoing total parenteral nutrition. The correlations between plasma taurine, other amino acid levels, parenteral substrate doses and metabolic and cardiorespiratory variables were assessed by regression analysis. Post-traumatic hypotaurinemia was followed by partial recovery toward less abnormal values when sepsis developed. Levels of taurine were directly and significantly related to levels of glutamate, aspartate, beta-alanine and phosphoethanolamine (and unrelated to other amino acids). Levels of these amino acids increased simultaneously with increasing doses of leucine, isoleucine and valine in total parenteral nutrition. Decreasing taurine was associated with increasing lactate, arteriovenous O(2) concentration difference and respiratory index, and with decreasing cholesterol and cardiac index. These results characterize the relationships between plasma taurine and other amino acid levels in sepsis, provide evidence of amino acid interactions that may support taurine availability and show more severe decreases in plasma taurine with the worsening of metabolic and cardiorespiratory patterns.

Adult↗
PubMed1999

Pathophysiologic correlates of hypocholesterolemia in critically ill surgical patients.

OBJECTIVE: To assess correlates of hypocholesterolemia in moderate to critical surgical illness. DESIGN: Prospective analysis of laboratory and clinical data. SETTING: Department of surgery in a university hospital. PATIENTS: 135 patients undergoing uncomplicated abdominal surgery or with sepsis, liver failure, hemorrhage, severe cholestasis, or multiple organ dysfunction syndrome (MODS). INTERVENTIONS: Surgical and/or medical therapy according to clinical status. MEASUREMENTS AND MAIN RESULTS: Determinations of total cholesterol, additional variables, and clinical data. Cholesterol decreased after surgery, in sepsis, liver failure, acute hemorrhage, and MODS and increased in cholestasis. Hypocholesterolemia correlated with decreases in plasma proteins and indices of hepatic protein synthetic adequacy, with hemodilution from blood loss, and was moderated or prevented by cholestasis. CONCLUSIONS: These results help to explain the dynamics of the development, clinical relevance, and negative prognostic value of hypocholesterolemia in critical illness.

Cholesterol↗
PubMed1999

Quantitative assessment of changes in blood CO(2) tension mediated by the haldane effect.

Adequate assessment of circulatory and gas-exchange interactions may involve the quantification of the Haldane effect (HE) and of the changes in blood PCO(2) mediated by changes in Hb-O(2) saturation and O(2)-linked CO(2) binding. This is commonly prevented by the complexity of the involved calculations. To simplify the task, a large series of patient measurements has been processed by regression analysis, thus developing an accurate fit for this quantification (v-a) PCO(2)HE + 0.460 [(a-v) HbO(2)]0.999e0.015(PvCO(2))-0.852(Hct) (n = 247, r(2) = 0. 99, P << 0.001), where (v-a)PCO(2 HE) is the reduction in venous PCO(2) (Pv(CO(2)), Torr) allowed by the chemical binding of CO(2) in blood due to the HE (Torr), (a-v)HbO(2) is the arteriovenous difference in Hb-bound O(2) (ml/dl), and Hct is hematocrit fraction. Values of (v-a)PCO(2 HE) estimated by this expression compared well with the results of previously published experiments. This formula is useful in assessing the impact of HE on Pv(CO(2)) and venoarterial PCO(2) gradient and the survival advantage offered by HE in extreme conditions. Use may be extended to all investigative and clinical settings in which changes in blood O(2) saturation and O(2)-linked CO(2) binding must be converted into the corresponding changes in dissolved CO(2) and PCO(2).

Blood Circulation↗
PubMed1998

Computer-assisted analysis of the impact of respiratory quotient on blood CO2 tension and pH changes.

A computer model for the accurate quantification of blood gas exchange components was used to assess the impact of respiratory quotient (RQ) on venoarterial CO2 tension and pH differences over a large group of patient measurements. The combined use of measured and computer-generated data has shown that, for any given increase in blood CO2 concentration (i.e., when the arterial blood becomes venous), the associated increase in CO2 tension and decrease in pH are inversely related to the RQ, and that this relationship is mediated by the Haldane effect. These results are useful for a through understanding of blood gas and metabolic interactions in normal and abnormal states, and for improving the interpretation of changes in venoarterial CO2 tension gradient in clinical monitoring.

Arteries↗
PubMed1997

The relationship between oxygen extraction and venous pH in sepsis.

This study was performed to quantify the impact of Haldane effect (HE) on the relationship between O2 extraction (O2Ex; mL O2/dL blood) and venous pH in 247 measurements performed in 91 septic patients (73 patients with intra-abdominal sepsis, 11 with retroperitoneal abscesses, 6 with severe cholangitis, and 1 with gangrenous fasclitis). The severity of sepsis varied from relatively compensated to extremely diseased conditions. This allowed a detailed assessment of the impact of HE over a wide range of cardiorespiratory and metabolic abnormalities. A recently developed model was used to quantify blood CO2 exchange and Haldane relationships and, in particular, the buffering of venous pH allowed by O2Ex (O2-linked H+ binding) on the basis of arterial and mixed venous blood gas measurements. Arterio-venous pH difference (a-vDpH) was .033 +/- .024 (mean +/- SD). It increased with venoarterial CO2 concentration difference (v-aDCO2; mL CO2/dL blood), but the increase was moderated by a simultaneous increase in O2Ex, as the likely consequence of HE: a-vDpH = .006 + .017 (v-aDCO2) - .009 (O2Ex) [r2 = .96, p < < .001]. To confirm this, the moderation of a-vDpH allowed by the HE (DpH) was calculated. A first component, due to O2-linked H+ binding, had a value of .016 +/- .012, and a second component, due to the Haldane-mediated reduction in venous CO2 tension and plasma carbonic acid concentration, had a value of .019 +/- .006. Their sum (total DpH) was .033 +/- .017 and was related directly and strongly to O2Ex: DpH = -.002 + .009 (O2Ex) [r2 = .85, p < < .001], thus confirming the quantitative impact of HE in moderating the decrease in venous pH relative to arterial pH. The loss of this effect was responsible for the larger decreases in venous pH observed in hypodynamic patients developing impaired O2Ex. These results allow an easy quantification of the Haldane component, separated from the other components affecting pH, and are also useful for assessing the protective role exerted by HE against excessive decreases in venous pH in circulatory failure.

Abdomen↗
PubMed1997

[The branched-chain amino acids].

Branched-chain amino acids (BCAA: leucine, isoleucine and valine) are not just structural constituents of proteins, but have ''pharmacologic'' properties, known for several years: BCAA are catabolized mainly in muscle; can be oxidized with energy production, being nitrogen donors for other amino acids; regulate protein synthesis and degradation; modulate metabolism of neuroactive mediators. These properties make the clinical use of BCAA particularly suitable in critical conditions such as liver cirrhosis, sepsis, surgical or nonsurgical trauma, acute renal failure, acute pancreatitis, cancer, in which energy production from conventional substrates is altered and, at the same time, reduction of protein catabolism and enhancement of synthetic processes is advisable. Recently, the changes of plasma aminoacidograms induced by the administration of high-dose BCAA in sepsis have been better detailed: 1) a tendency to normalization of high levels of proline and of other amino acids transported intracellularly by transport system ''A''; 2) less relevant reduction of the levels of other amino acids; 3) increase of the levels of taurine, glutamate and aspartate; more complex interactions with specific amino acids. These changes, and changes of other variables, reconfirm in part some well-known properties of BCAA, and are also objective indicators of an improvement of the metabolic abnormalities of sepsis induced by BCAA administration. In sepsis and in other stress conditions it is recommended to administer, within balanced parenteral nutritional regimens, AA solutions with a 35-50% BCAA concentration.

English Abstract↗
PubMed1997

[Medium-chain triglycerides in artificial nutrition].

Medium Chain Triglycerides (MCT) are lipids which are commonly present in nature, for instance in milk and in some vegetable oils. The MCT molecule is composed of glycerol esterified with saturated linear-chain fatty acids containing 6 to 12 carbon atoms (MCFA: Medium Chain Fatty Acids: C(6:0), esanoic acid; C(8:0), octanoic acid; C(10:0), decanoic acid; C(12:0), dodecanoic acid). MCT for clinical use are currently obtained from vegetable fat through industrial processing. The large interest for MCT in clinical nutrition is due to unique physico-chemical, biochemical and metabolic features, which characterize MCT compared to conventional lipids (LCT: Long Chain Triglycerides). In particular, MCT represent a source of rapidly, fully available and ''high density'' energy, which makes their use very advantageous and suitable in a wide range of clinical situations, from the premature newborn to the adult patient. In addition to the MCT oil, known to physicians and nutritionists since the 1950s, and to the many commercially available MCT-containing compounds for oral-enteral use, in the last years it has become possible also to administer MCT-containing emulsions in parenteral nutrition. This has allowed to improve further knowledge of the effects of MCT, expanding the indications for use, often as a ''first-choice'' substrate in different types of critically ill patients.

English Abstract↗
PubMed1995

[The tissue characterization of focal liver lesions by color Doppler echography].

To investigate color-Doppler capabilities in tissue characterization, 47 hepatic lesions were studied. The real-time morphologic appearance of the lesions was studied first and then color flow images were acquired, assessing color areas and the distribution of blood flow for each lesion. For quantitative Doppler study, the color Doppler signal was used as a guide to obtain the Doppler spectrum and to measure flow velocities and pulsatility index (PI) values. Data were plotted and analyzed statistically; criteria for differentiating malignant from benign hepatic tumors and the patterns suggestive of either condition were proposed. Absolutely no Doppler signal was observed in avascular or necrotic lesions and in low-flow tumors, e.g., metastases (10%) and hemangiomas (63%). Many color signals at the periphery and within tumor masses were observed in highly vascular lesions, e.g., hepatocellular carcinomas (60%) and focal nodular hyperplasia (80%). Multiple afferent vessels and a "basket-like" pattern were detected in a high percentage of hepatocellular carcinomas. High-flow velocities (> 0.85 m/s perilesional systolic velocity and > 0.80 m/s intralesional systolic velocity) and high PI values (> 1.5 perilesional PI and > 0.90 intralesional PI) are suggestive of malignancy. Particularly, 0.90 intralesional PI cutoff value exhibits 89% specificity and 82% sensitivity in benign versus malignant differential diagnosis. Our results suggest that color-Doppler US is a useful means of studying the hemodynamics of hepatic tumors which increases US diagnostic accuracy.

Diagnosis, Differential↗
PubMed1994

[The surgical risk of liver resections for neoplasms in the elderly patient].

For patients who are candidates for surgical resection of the liver, advanced age has, for many years, been considered to be a limiting factor or has precluded intervention. More recently, improvements in diagnostic, surgical and anaesthetic techniques and the increase in the average age of the population have gradually broadened the indications for hepatic resection in elderly patients. The factors for reappraisal of the surgical risk of liver resection in elderly patients are discussed here. Comparative data are also presented on the mortality, morbidity and post-operative changes in blood chemistry parameters in 90 patients who underwent hepatic resection: 33 patients over 65 years of age (group A) and 57 under 65 years (group B). In group A, compared to group B, mortality (3% versus 5%) and the percentage of patients with post-operative complications (27% versus 37%) were not significantly different. The incidence of post-operative complications correlated more closely with specific risk factors (elevated pre-operative "ASA score" from associated disease) than with age itself. Analysis of the regressions did not reveal important relationships between age and changes in the blood chemistry parameters. These results help to support the idea that advanced age alone is not now an absolute contra-indication to major liver resection.

Age Distribution↗
PubMed1994

[The choice of substrates in total parenteral nutrition].

This review contains a full outline on the choice of substrates in total parenteral nutrition (NPT). The basic properties of "conventional" substrates (glucose, long chain triglyceride-containing fat, common amino acid mixtures) are used to outline the general principles for NPT support in normal conditions and in stress (surgical and nonsurgical trauma, sepsis). Without taking into account factors which are not strictly metabolic (vascular access, local availability of products, costs), particular attention is then paid to "non-conventional" substrates and substrate mixtures, including some under study, with specific reference to properties and features which may motivate their choice.

Amino Acids↗
PubMed1993

Calculation of venoarterial CO2 concentration difference.

Quantitative relationships in CO2 transport and exchange processes were combined for use as the basic components of an original mathematical model for the calculation of venoarterial blood CO2 concentration difference (v-aDCO2). This is calculated as the sum of the increment in CO2 concentration (CCO2) related to the increase in CO2 tension (delta P) from arterial to venous value at constant O2 saturation (delta CCO2/delta P) and of the increment in CO2 concentration related to the decrease in O2 saturation (delta S) from arterial to venous value at constant CO2 tension (delta CCO2/delta S). The newly developed relationships correlated well with the experimental data from which they were derived (r2 = 0.94-0.99). The results provided by the model compared remarkably well with the results of previously published measurements (r2 = 0.96-0.99). This new model allows one to overcome some of the limitations implicit in previously available methods and provides a useful tool for the assessment and monitoring of hemodynamic, metabolic, and O2-CO2 exchange patterns in whole body and regional vascular beds.

Arteries↗
PubMed1991

Leucine dose response in the reduction of urea production from septic proteolysis and in the stimulation of acute-phase proteins.

The administration of branched-chain amino acids (BCAAs) has been proved useful in reducing both urea nitrogen production and muscle proteolysis in trauma patients with sepsis, but the optimum infusion rate to achieve these effects is still in question. In this prospective randomized study, a group of 16 posttrauma patients with sepsis received a branched chain-enriched (BCAA = 49.4%) amino acid mixture (8 patients; 120 observations) or a standard amino acid infusion (BCAAs = 15.5%; 8 patients; 227 observations). Total calories, percent lipid calories, and amino acid nitrogen administration were not different in the two groups. Each patient was studied at 8-hour intervals for the plasma levels of amino acids, six hepatic acute-phase proteins, albumin, and other metabolic parameters, including urinary urea nitrogen and 3-methylhistidine excretion. The total intake of each amino acid and its clearance were calculated and the dose of leucine during each 8-hour period was related to the leucine clearance, plasma acute-phase protein levels, and the urinary production of urea and 3-methylhistidine, as an indicator of proteolysis. The results show a significant (r2 = 0.691; p less than 0.0001) reduction of urea nitrogen production and proteolysis as a function of the increase in leucine dose. The identification of a critical mean rate of leucine infusion has been derived from the analysis of the significant linear correlation between leucine intake and leucine clearance (r2 = 0.594; p less than 0.0001). Significant positive correlations between the leucine intake dose and the platelet count (r2 = 0.402; p less than 0.0001), the plasma fibrinogen level (r2 = 0.218; p less than 0.0001), and the regression-derived sum of six acute-phase proteins plus albumin (r2 = 0.696; p less than 0.0001) were found. The increase in leucine clearance was progressively less marked above a mean daily leucine intake rate of 1.4 mumol/kg/min, which also appeared to be the dose level that maximized the acute-phase protein and coagulation effects and reduced proteolysis and urea nitrogen production, suggesting that this is a critical BCAA infusion rate at which an optimum leucine effect occurs. From these data a BCAA (leucine) dose nomogram has been derived.

Acute-Phase Proteins↗